WO2025234404A1 - Pyrimidine-containing condensed ring compound and use thereof - Google Patents

Abstract

The present invention addresses the problem of providing a compound that has a pyrimidine structure and that exhibits an excellent effect against malignant tumors.　The present invention relates to a pyrimidine-containing condensed ring compound represented by general formula (1) (in the formula, the Ar ring group represents a monocyclic or condensed bicyclic aromatic heterocyclic group or a C6-10 aromatic hydrocarbon group; the heterocycle represents a pyrole ring, a pyrrolidine ring, a thiophene ring, a furan ring, a pyrazole ring, or a pyridine ring; A, B, C, and D are identical to each other or different from each other and each represent C, CH, or N, up to two of A, B, C, and D are N, and the dashed lines in this ring indicate that there may be a double bond (where, when a dashed line is a double bond and A, B, C, or D is N, R¹, R², R³, and R⁴ are absent on said N); R¹, R², R³, and R⁴ are identical to each other or different from each other and each represent a hydrogen atom, an alkyl group, or the like; R⁵ and R⁶ are identical to each other or different from each other and each represent a hydrogen atom, a halogen atom, or the like; R⁷ and R⁸ are identical to each other or different from each other and each represent a hydrogen atom, a halogen atom, or the like; and n represents a number of 0 or 1), a salt thereof, or a solvate of these.

Description

Pyrimidine-containing fused ring compounds and their uses

The present invention relates to a pyrimidine-containing fused ring compound and a pharmaceutical containing the same.

Among the drugs used to treat malignant tumors, molecularly targeted drugs have been developed, which are compounds that inhibit molecules involved in cell proliferation, but the target molecules are becoming increasingly diverse. For example, tyrosine kinase inhibitors, FLT tyrosine kinase inhibitors, anaplastic lymphoma kinase (ALK) inhibitors, Janus kinase inhibitors, PARP inhibitors, and Raf kinase inhibitors have been developed.

Meanwhile, compounds that have been reported to have a pyrimidine structure include a PI3K inhibitor with a purine structure (Patent Document 1), a p97 complex inhibitor with a pyrimidine fused ring structure (Patent Document 2 and Non-Patent Document 1), compounds with a pyrimidine structure (Non-Patent Documents 2 and 3 and Patent Document 3), and compounds in which morpholine is bound to a pyrimidine skeleton (Patent Document 4).

WO 2010/138589 WO 2014/15291 Korean Patent Application Publication No. 2021/25188 Japanese Patent No. 3836436

Journal of Medicinal Chemistry, 2015, vol. 58(24), p. 9480-9497 Applied Organometallic Chemistry, 2016, vol. 30(11), p. 949-953 Synlett, 2016, vol. 27(11), p. 1743-1747

However, these compounds having a pyrimidine skeleton are not used as therapeutic agents for malignant tumors, or their anti-malignant tumor activity is not sufficient.
Therefore, an object of the present invention is to provide a compound having a pyrimidine structure that has excellent anti-malignant tumor effects.

The inventors therefore synthesized numerous compounds with a pyrimidine skeleton and tested their anti-cancer activity. As a result, they discovered that compounds in which an aromatic heterocyclic group or aromatic hydrocarbon group is bound to a pyrimidine-containing fused ring possess excellent anti-cancer activity, leading to the completion of the present invention.

That is, the present invention provides the following inventions [1] to [8].
[1] The following general formula (1)

(In the formula, the Ar ring group represents a monocyclic or bicondensed ring aromatic heterocyclic group or an aromatic hydrocarbon group having 6 to 10 carbon atoms;
Het ring represents a pyrrole ring, a pyrrolidine ring, a thiophene ring, a furan ring, a pyrazole ring, or a pyridine ring;
A, B, C, and D are the same or different and represent C, CH, or N, and the number of N among A, B, C, and D is up to two, and the dashed line in this ring indicates that a double bond may be present (here, when the dashed line represents a double bond and A, B, C, or D is N, R ¹ , R ² , R ³ , and R ⁴ do not exist on the N);
R ¹ , R ² , R ³ and R ⁴ are the same or different and each represent a hydrogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a hydroxy group, a hydroxyalkyl group, an alkanoyl group or an alkoxycarbonyl group;
^R5 and ^R6 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, a halogenoalkyl group, a hydroxyalkyl group, an alkanoyl group, a benzoyl group, an oxo group, or a carbamoyl group optionally substituted with one or two alkyl groups;
^R7 and ^R8 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a hydroxy group, or an amino group optionally substituted with one or two alkyl groups;
n represents the number 0 or 1)
A pyrimidine-containing fused ring compound represented by the following formula:
[2] The pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to [1], wherein the ring group Ar is a pyrrolopyrimidyl group, a pyrrolopyridyl group, a dihydropyrrolopyridyl group, a tetrahydropyridopyridyl group, a tetrahydroquinolyl group, a tetrahydroisoquinolyl group, an ethylenedioxyphenyl group, an ethylenedioxypyridyl group, an indolyl group, an isoindolyl group, an indolinyl group, an isoindolinyl group, a pyridyl group, a pyrimidyl group, an imidazolyl group, a pyrazolyl group, a pyrrolyl group, a thienyl group, a furyl group, an indenyl group, a naphthyl group, or a phenyl group.
[3] The pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to [1] or [2], wherein the ring containing A, B, C, and D is a benzene ring, a cyclohexane ring, a cyclopentane ring, a pyridine ring, a pyrimidine ring, or a piperidine ring.
[4] A pharmaceutical composition comprising the pyrimidine-containing fused ring compound according to any one of [1] to [3], a salt thereof, or a solvate thereof, and a pharmaceutically acceptable carrier.
[5] A therapeutic agent for malignant tumors, comprising as an active ingredient the pyrimidine-containing fused ring compound, a salt thereof, or a solvate thereof according to any one of [1] to [3].
[6] The pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to any one of [1] to [3] for use in the treatment of a malignant tumor.
[7] Use of the pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to any one of [1] to [3] for the manufacture of a therapeutic agent for malignant tumors.
[8] A method for treating malignant tumors, comprising administering the pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to any one of [1] to [3].

The pyrimidine-containing fused ring compound represented by the general formula (1), its salt, or a solvate thereof exhibits excellent growth inhibitory activity against various cancer cells and is therefore useful as a therapeutic agent for malignant tumors.

FIG. 1 shows how GI ₅₀ was determined in Test Example 1 (in vitro antitumor activity test). This figure shows the malignant tumor-reducing effect of compound 32 on the breast cancer-derived cell line MDA-MB-468 in Test Example 2 (in vivo antitumor activity test). This figure shows the effect of compound 32 on changes in mouse body weight in Test Example 2 (in vivo antitumor activity test).

Terms used in this specification are used in the sense commonly used in the relevant field unless otherwise specified.

In this specification, hydrocarbons are a general term for compounds made up only of carbon atoms and hydrogen atoms, and are broadly classified into chain hydrocarbons and cyclic hydrocarbons based on their molecular structure, and are further subdivided into aliphatic hydrocarbons, alicyclic hydrocarbons, aromatic hydrocarbons, etc. Aromatic hydrocarbons are hydrocarbons that are composed of a single ring or multiple rings and exhibit aromaticity.
In the present invention, aromatic hydrocarbons having 6 to 10 carbon atoms are preferably used, and specific examples thereof include benzene, indene, and naphthalene.
The alkyl group in the present invention includes saturated aliphatic hydrocarbons and saturated alicyclic hydrocarbons. Specific examples include linear or branched alkyl groups having 1 to 6 carbon atoms, and linear or branched alkyl groups having 1 to 4 carbon atoms are more preferred.

As used herein, a heterocyclic compound refers to a cyclic compound containing at least two different elements in the ring, and in the present invention, refers to a cyclic compound containing one or more atoms selected from nitrogen, oxygen, and sulfur atoms in addition to carbon atoms. An aromatic heterocyclic compound refers to a compound that exhibits aromaticity and contains one or more atoms selected from nitrogen, oxygen, and sulfur atoms in addition to carbon atoms. Furthermore, when referring to a two-condensed-ring aromatic heterocyclic group, it is sufficient that one of the condensed rings is an aromatic ring.
In the present invention, non-aromatic heterocyclic compounds such as pyrrolidine and piperidine may also be used.

In this specification, the term "alkoxy group" refers to a structure in which the alkyl group is bonded to an oxygen atom. Specific examples include linear or branched alkoxy groups having 1 to 6 carbon atoms, and linear or branched alkoxy groups having 1 to 4 carbon atoms are more preferred.
The alkanoyl group is a functional group formed by removing a hydroxy group from an alkanoic acid, and specific examples thereof include linear or branched alkanoyl groups having 1 to 6 carbon atoms, and linear or branched alkanoyl groups having 1 to 4 carbon atoms are more preferred.
A carbamoyl group is a monovalent group represented by _-CONH2 . An oxo group is a group represented by =O. Examples of halogen atoms include fluorine atoms, chlorine atoms, bromine atoms, and iodine atoms.

One aspect of the present invention is a compound represented by the following general formula (1):

(In the formula, the Ar ring group represents a monocyclic or bicondensed ring aromatic heterocyclic group or an aromatic hydrocarbon group having 6 to 10 carbon atoms;
Het ring represents a pyrrole ring, a pyrrolidine ring, a thiophene ring, a furan ring, a pyrazole ring, or a pyridine ring;
A, B, C, and D are the same or different and represent C, CH, or N, and the number of N among A, B, C, and D is up to two, and the dashed line in this ring indicates that a double bond may be present (here, when the dashed line represents a double bond and A, B, C, or D is N, R ¹ , R ² , R ³ , and R ⁴ do not exist on the N);
R ¹ , R ² , R ³ and R ⁴ are the same or different and each represent a hydrogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a hydroxy group, a hydroxyalkyl group, an alkanoyl group or an alkoxycarbonyl group;
^R5 and ^R6 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, a halogenoalkyl group, a hydroxyalkyl group, an alkanoyl group, a benzoyl group, an oxo group, or a carbamoyl group optionally substituted with one or two alkyl groups;
^R7 and ^R8 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a hydroxy group, or an amino group optionally substituted with one or two alkyl groups;
n represents the number 0 or 1)
The pyrimidine-containing fused ring compound is represented by the following formula (I):

In general formula (1), the Ar ring group represents a monocyclic or two-condensed ring aromatic heterocyclic group or an aromatic hydrocarbon group having 6 to 10 carbon atoms. The monocyclic or two-condensed ring aromatic heterocyclic group is preferably a monocyclic or two-condensed ring aromatic heterocyclic group containing, in addition to carbon atoms, one or more atoms selected from a nitrogen atom, an oxygen atom, and a sulfur atom. In addition, when referring to a two-condensed ring aromatic heterocyclic group, it is sufficient that one of the condensed rings is an aromatic ring. The total number of elements forming the monocyclic or two-condensed ring is preferably 5 to 10. The number of heteroatoms selected from a nitrogen atom, an oxygen atom, and a sulfur atom is preferably 1 to 3.
Examples of the aromatic heterocyclic group include a pyrrolopyrimidyl group, a pyrrolopyridyl group, a dihydropyrrolopyridyl group, a tetrahydropyridopyridyl group, a tetrahydroquinolyl group, a tetrahydroisoquinolyl group, an ethylenedioxyphenyl group, an ethylenedioxypyridyl group, an indolyl group, an isoindolyl group, an indolinyl group, an isoindolinyl group, a pyridyl group, a pyrimidyl group, an imidazolyl group, a pyrazolyl group, a pyrrolyl group, a thienyl group, and a furyl group. Among these, a pyrrolopyridyl group, a dihydropyrrolopyridyl group, a tetrahydropyridopyridyl group, a tetrahydroisoquinolyl group, an ethylenedioxyphenyl group, an ethylenedioxypyridyl group, an indolinyl group, an isoindolinyl group, a pyridyl group, a pyrimidyl group, an imidazolyl group, a pyrazolyl group, a pyrrolyl group, a thienyl group, and a furyl group are more preferred.
Examples of the aromatic hydrocarbon group having 6 to 10 carbon atoms include a phenyl group, an indenyl group, and a naphthyl group, with a phenyl group being more preferred.

The Het ring in the general formula (1) represents a pyrrole ring, a pyrrolidine ring, a thiophene ring, a furan ring, a pyrazole ring, or a pyridine ring, and among these, a pyrrole ring, a pyrazole ring, or a pyridine ring is more preferred.
A more preferred structure of the Het ring is the following structure: The bond in the following structure is part of the pyrimidine ring adjacent to the Het ring.

A, B, C, and D are the same or different and represent C, CH, or N, and the number of N among A, B, C, and D is up to two, and the dashed line in this ring indicates that a double bond may be present (here, when the dashed line represents a double bond and A, B, C, or D is N, R ¹ , R ² , R ³ , and R ⁴ do not exist on the N).
Specific examples of the ring containing A, B, C, and D include a benzene ring, a cyclohexane ring, a cyclopentane ring, a pyridine ring, a pyrimidine ring, and a piperidine ring. A more preferred structure of this ring is the following structure: The bond in the following structure is part of the imidazole ring adjacent to the ring containing A, B, C, and D.

R ¹ , R ² , R ³ and R ⁴ are the same or different and each represents a hydrogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a hydroxy group, a hydroxyalkyl group, an alkanoyl group or an alkoxycarbonyl group.
Here, examples of the alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms, and more preferably linear or branched alkyl groups having 1 to 4 carbon atoms. Specific examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and an n-butyl group.
Examples of the alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms, and more preferably linear or branched alkoxy groups having 1 to 4 carbon atoms. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, an n-propyloxy group, and an isopropyloxy group.
Examples of the alkoxyalkyl group include a C1-4 alkoxy-C1-4 alkyl group, and specific examples thereof include a methoxymethyl group and an ethoxyethyl group.
The hydroxyalkyl group is preferably a hydroxy C1-4 alkyl group, more preferably a hydroxymethyl group, a 2-hydroxyethyl group, or the like.
Examples of the alkanoyl group include linear or branched alkanoyl groups having 1 to 6 carbon atoms, and more preferably linear or branched alkanoyl groups having 1 to 4 carbon atoms. Specific examples include an acetyl group and a propionyl group.
The alkoxycarbonyl group is preferably a C1-4 alkoxycarbonyl group, such as a methoxycarbonyl group or an ethoxycarbonyl group.
In R ¹ , R ² , R ³ and R ⁴ , one element may be substituted with two substituents.

^R5 and ^R6 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, a halogenoalkyl group, a hydroxyalkyl group, an alkanoyl group, a benzoyl group, an oxo group, or a carbamoyl group optionally substituted with one or two alkyl groups.
Here, examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Examples of the alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms, and more preferably linear or branched alkyl groups having 1 to 4 carbon atoms. Specific examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and an n-butyl group.
Examples of the halogenoalkyl group include a halogeno-C1-4 alkyl group. Examples of the halogen atom that is a substituent of this alkyl group include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Specific examples of the halogenoalkyl group include a chloromethyl group, a dichloromethyl group, a trichloromethyl group, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, and a fluoroethyl group.
The hydroxyalkyl group is preferably a hydroxy C1-4 alkyl group, more preferably a hydroxymethyl group, a 2-hydroxyethyl group, or the like.
Examples of the alkanoyl group include linear or branched alkanoyl groups having 1 to 6 carbon atoms, and more preferably linear or branched alkanoyl groups having 1 to 4 carbon atoms. Specific examples include an acetyl group and a propionyl group.
As the carbamoyl group optionally substituted with one or two alkyl groups, a carbamoyl group optionally substituted with one or two C1-4 alkyl groups is preferred, and a carbamoyl group, a methylcarbamoyl group, a dimethylcarbamoyl group, an ethylcarbamoyl group, a diethylcarbamoyl group, etc. are more preferred.

^R7 and ^R8 may be the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a hydroxy group, or an amino group which may be substituted with one or two alkyl groups.
Here, examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Examples of the alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms, and more preferably linear or branched alkyl groups having 1 to 4 carbon atoms. Specific examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and an n-butyl group.
Examples of the alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms, and more preferably linear or branched alkoxy groups having 1 to 4 carbon atoms. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, an n-propyloxy group, and an isopropyloxy group.
Examples of the alkoxyalkyl group include a C1-4 alkoxy-C1-4 alkyl group, and specific examples thereof include a methoxymethyl group and an ethoxyethyl group.
As the amino group which may be substituted with one or two alkyl groups, an amino group which may be substituted with one or two C1-4 alkyl groups is preferred, and an amino group, a methylamino group, a dimethylamino group, an ethylamino group, a diethylamino group, etc. are more preferred.

In the general formula (1), the Ar ring group is a pyrrolopyrimidyl group, a pyrrolopyridyl group, a dihydropyrrolopyridyl group, a tetrahydropyridopyridyl group, a tetrahydroquinolyl group, a tetrahydroisoquinolyl group, an ethylenedioxyphenyl group, an ethylenedioxypyridyl group, an indolyl group, an isoindolyl group, an indolinyl group, an isoindolinyl group, a pyridyl group, a pyrimidyl group, an imidazolyl group, a pyrazolyl group, a pyrrolyl group, a thienyl group, a furyl group, or a phenyl group;
The Het ring is a pyrrole ring, a pyrazole ring, or a pyridine ring;
More preferred are compounds in which the ring containing A, B, C and D is a benzene ring, a cyclohexane ring, a cyclopentane ring, a pyridine ring, a pyrimidine ring or a piperidine ring.
Furthermore, the Ar ring group is a pyrrolopyridyl group, a dihydropyrrolopyridyl group, a tetrahydropyridopyridyl group, a tetrahydroisoquinolyl group, an ethylenedioxyphenyl group, an ethylenedioxypyridyl group, an indolinyl group, an isoindolinyl group, a pyridyl group, a pyrimidyl group, an imidazolyl group, a pyrazolyl group, a pyrrolyl group, a thienyl group, a furyl group, or a phenyl group;
The Het ring is a pyrrole ring, a pyrazole ring, or a pyridine ring;
More preferred are compounds in which the ring containing A, B, C and D is a benzene ring, a cyclohexane ring, a cyclopentane ring, a pyridine ring, a pyrimidine ring or a piperidine ring.

Among the compounds of the general formula (1), more preferred specific compounds are shown below.
2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine 5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluoroaniline 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-4-(5-fluoropyridin-3-yl)-7-methyl-7H-pyrrolo[2, 3-d]pyrimidine, 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(1H-pyrrol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine, 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(pyrimidin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine, 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(pyridin-4-yl)-7H-pyrrolo[2,3- d]pyrimidine, 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine, 2-(1H-benzo[d]imidazol-1-yl)-4-(furan-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine, 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidine 7-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3-dihydro-1,4-dioxino[2,3-b]pyridine; 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(6-methylpyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(2-methylpyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol; 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-methylaniline; 5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl- 7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluoro-N-methylaniline; 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-4-(3,4-dimethoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 3-(2 -(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylaniline, 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol, 6-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4 -tetrahydroisoquinoline·7-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline·3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine·2-(1H-benzo[d]imidazole- 1-yl)-4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine; 5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine- 4-yl)-N,N-dimethylpyridin-3-amine, 4-(4-fluorophenyl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine, 7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline, 2-methyl-7-(7-methyl-2 -(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline; 4-(isoindolin-5-yl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine; 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(2-methylisoindolin) 6-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline; 2-methyl-6-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine 7-methyl-2-(4-methyl -1H-benzo[d]imidazol-1-yl)-4-(1-methylindolin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine; 7-methyl-3-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5,6,7,8-tetrahydro-1,7-naphthyridine; 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4- (1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine; 5-(5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-3-amine; 5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1 -methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine; 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine; 5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methyl 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(3-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 5-(2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline; 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(5-(methoxymethyl)pyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro 7-methyl-4-(2-methylpyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine. 5-(2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine. 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-fluoro -7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-4-(1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-7-ethyl-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)- 2-(1H-benzo[d]imidazol-1-yl)-7-(difluoromethyl)-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-7-(difluoromethyl)-4-(pyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-7-(difluoromethyl)-4-(2-methylpyridin-4-yl)-7H-pyrrolo[ 2,3-d]pyrimidine, (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methanol, 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine, (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-7-carboxamide; 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-7-carboxamide 2-(1H-benzo[d]imidazol-1-yl)-6,7-dimethyl-4-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine; 6-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine; 6-(1H-benzo[d]imidazole- 1-yl)-1-methyl-4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidine; 5-(6-(1H-benzo[d]imidazol-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine; 3-(6-(1H-benzo[d]imidazol-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine -dimethylaniline; 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)furo[3,2-d]pyrimidine; 5-(2-(1H-benzo[d]imidazol-1-yl)furo[3,2-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline; 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)furo[3,2-d]pyrimidine; 2-(1H-benzo[d] 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)furo[3,2-d]pyrimidine, 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)pyrido[2,3-d]pyrimidine, 2-(1H-benzo[d]imidazol-1-yl)-4-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidine, 2-(1H-benzo[d]imidazol-1-yl)-4-(3,4-di 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one; 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidine; 5-(2-(1H-benzo[d]imidazol-1-yl)-6-methyl- 6H-pyrrolo[3,4-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline; 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)thieno[3,4-d]pyrimidine; 5-(2-(1H-benzo[d]imidazol-1-yl)thieno[3,4-d]pyrimidine 2-(1H-benzo[d]imidazol-1-yl)-4-(1-methyl-1H-pyrazol-4-yl)thieno[3,4-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine; 2-(1H-benzo[d]imidazol-1-yl)-4 -(4-Fluorophenyl)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine; 1-(2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)ethanone; 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-5-ol; methyl 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazole-4-carboxylate; 1-(1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-4-yl)ethan-1-one; 2-(4-ethyl-1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine; 4-(4-fluorophenyl)-2-(4-(methoxymethyl)-1H-benzo[d]imidazole-1 -yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine, 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-b]pyridine, 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-c]pyridine, 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3H-imidazo[4,5-b]pyridine, 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3H-imidazo[4,5-b]pyridine 2-yl)-3H-imidazo[4,5-c]pyridine, 4-(4-fluorophenyl)-7-methyl-2-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine, 2-(5,6-dihydrocyclopenta[d]imidazol-1(4H)-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine, 9-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-9H-purine, 7-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl) 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine; 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine; 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine

The pyrimidine-containing fused ring compound represented by general formula (1) (hereinafter also referred to as compound (1) of the present invention) may take the form of a pharmaceutically acceptable acid addition salt. Examples of the acid addition salt include inorganic acid salts such as hydrochloride, sulfate, hydrobromide, nitrate, and phosphate, and organic acid salts such as acetate, oxalate, propionate, glycolate, lactate, pyruvate, malonate, succinate, maleate, fumarate, malate, tartrate, citrate, benzoate, cinnamate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, and salicylate.
The compound (1) of the present invention or a salt thereof may be in the form of a solvate such as a hydrate or an ethanol solvate.
When the compound (1) of the present invention has an asymmetric carbon atom in its structure, it exists in the form of isomers derived from the asymmetric carbon atom and mixtures thereof (racemates), all of which are included in the present invention.

Compound (1) of the present invention, its salt, or a solvate thereof can be prepared, for example, according to the following reaction scheme:

(In the reaction formula, R ⁹ and R ¹⁰ represent a hydrogen atom, or R ⁹ and R ¹⁰ together with the two adjacent oxygen atoms form an alkylenedioxy group, and Ar ring group, Het ring, A to D, R ¹ to R ⁸ and n are the same as above.)
That is, compound (2) is cross-coupled (Suzuki-Miyaura coupling) with a boronic acid derivative (3) to obtain compound (4), which is then reacted with an imidazole derivative (5) to produce compound (1) of the present invention.
Depending on the type of the substituents R ¹ to R ⁸ , the substituents may be converted after these reactions.

The reaction of compound (2) with boronic acid derivative (3) is Suzuki-Miyaura coupling. The alkylenedioxy group in boronic acid derivative (3) may be a group derived from pinacol or trimethylene glycol.
The reaction may be carried out by adding water in the presence of a palladium catalyst such as palladium acetate, palladium chloride, bis(triphenylphosphine)palladium(II) dichloride, tetrakis(triphenylphosphine)palladium(0), tris(dibenzylideneacetone)dipalladium(0), or [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride, and a base such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, tripotassium phosphate, sodium methoxide, or potassium tert-butoxide. Examples of reaction solvents that can be used include toluene, hexane, xylene, dioxane, tetrahydrofuran, dimethoxyethane, dichloroethane, and N,N-dimethylformamide. The reaction may be carried out at a temperature of 50 to 200°C for approximately 5 minutes to 20 hours.

The reaction of compound (4) with imidazole derivative (5) is a Buchwald-Hartwig cross-coupling reaction.
The reaction may be carried out in the presence of a palladium catalyst such as palladium acetate, palladium chloride, or tris(dibenzylideneacetone)dipalladium(0), a bidentate ligand such as 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, or 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and a base such as sodium hydroxide, potassium hydroxide, tripotassium phosphate, sodium carbonate, potassium carbonate, or cesium carbonate. Examples of the reaction solvent include acetone, toluene, hexane, xylene, dioxane, tetrahydrofuran, dichloroethane, and N,N-dimethylformamide. The reaction may be carried out at a temperature of 50° C. to 200° C. for about 5 minutes to 20 hours.

Also, compound (1) of the present invention, its salt, or solvate thereof can be produced according to the following reaction scheme:

(In the reaction formula, Bn represents a benzyl group, Ts represents a p-toluenesulfonyl group, and Ar represents a ring group, Het represents a ring, A to D, R ¹ to R ¹⁰ and n are the same as above.)
That is, compound (2) is reacted with benzyl alcohol (BnOH) to obtain compound (6), which is then reacted with compound (5) to obtain compound (7). Compound (7) is reduced to compound (8), which is then reacted with p-toluenesulfonyl chloride (Ts-Cl) to obtain compound (9). Compound (9) is coupled with compound (3) to produce compound (1).

The reaction of compound (2) with benzyl alcohol can be carried out in the presence of a base such as sodium hydride. Reaction solvents that can be used include toluene, hexane, xylene, dioxane, tetrahydrofuran, dimethoxyethane, dichloroethane, and N,N-dimethylformamide. The reaction can be carried out under ice-cooling at temperatures ranging from 100°C for approximately 5 minutes to 10 hours.

The reaction between compound (6) and compound (5) is a Buchwald-Hartwig cross-coupling reaction, and can be carried out in the same manner as the reaction between compound (4) and compound (5) described above.

Compound (7) can be reduced to give compound (8). The reduction reaction can be carried out by contacting the compound with hydrogen in the presence of a catalyst such as palladium on activated carbon.
Compound (8) is then reacted with p-toluenesulfonyl chloride (Ts-Cl) to give compound (9). This reaction is preferably carried out in the presence of a base such as a tertiary amine.

Compound (1) can be obtained by coupling compound (9) with compound (3). This reaction is a Suzuki-Miyaura coupling reaction, and can be carried out in the same manner as the reaction between compound (2) and compound (3) described above.

After the reaction is complete, the resulting compound (1) of the present invention may be isolated as is, or may be isolated after conversion to an acid addition salt. If necessary, compound (1) of the present invention or a salt thereof may be separated and purified by conventional methods, such as extraction, concentration, neutralization, filtration, recrystallization, column chromatography, etc.

The compound (1), a salt thereof, or a solvate thereof thus obtained according to the present invention exhibits an excellent growth inhibitory effect against various cancer cells in vitro, and also exhibits an anti-malignant tumor effect against transplanted cancer cells in vivo, without exhibiting any toxicity such as significant weight loss, and is therefore useful as a therapeutic agent for malignant tumors.
Therefore, another aspect of the present invention is a pharmaceutical composition comprising the compound (1) of the present invention, a salt thereof, or a solvate thereof, and a pharmaceutically acceptable carrier.
Another aspect of the present invention is a therapeutic agent for malignant tumors, which comprises the compound (1) of the present invention, a salt thereof, or a solvate thereof as an active ingredient.
Another aspect of the present invention is compound (1), a salt thereof, or a solvate thereof for use in the treatment of malignant tumors.
Another aspect of the present invention is use of compound (1), a salt thereof, or a solvate thereof for the manufacture of a therapeutic agent for malignant tumors.
Another aspect of the present invention is a method for treating malignant tumors, which comprises administering compound (1) of the present invention, a salt thereof, or a solvate thereof.

The malignant tumor therapeutic agent and pharmaceutical composition of the present invention may contain compound (1), a salt thereof, or a solvate thereof as the active ingredient, and may further contain other anticancer agents, etc.

Types of malignant tumors (cancers) that can be treated with the pharmaceutical composition of the present invention include, for example, head and neck cancer, esophageal cancer, stomach cancer, colon cancer, rectal cancer, liver cancer, gallbladder and bile duct cancer, pancreatic cancer, lung cancer, breast cancer, ovarian cancer, cervical cancer, uterine cancer, kidney cancer, bladder cancer, prostate cancer, testicular tumors, bone and soft tissue sarcoma, leukemia, malignant lymphoma, multiple myeloma, skin cancer, and brain tumors.

The pharmaceutical composition of the present invention is particularly useful as a therapeutic agent for malignant tumors, and can typically contain pharmaceutically acceptable carriers, additives, etc. The dosage form of the pharmaceutical composition is not particularly limited and can be selected appropriately depending on the purpose of treatment. For example, it may be an oral agent, injection, suppository, ointment, inhalant, eye drops, nasal drops, patch, etc. Pharmaceutical compositions suitable for these dosage forms can be manufactured using known formulation methods.

When preparing oral solid dosage forms, compound (1), its salt, or a solvate thereof is mixed with an excipient, and optionally a binder, disintegrant, lubricant, colorant, flavoring agent, odorant, etc., and then tablets, coated tablets, granules, powders, capsules, etc. can be produced by conventional methods. Additives commonly used in the field may be used. For example, excipients include lactose, sucrose, sodium chloride, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, silicic acid, etc. Binders include water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropyl starch, methylcellulose, ethylcellulose, shellac, calcium phosphate, polyvinylpyrrolidone, etc. Disintegrants include dry starch, sodium alginate, powdered agar, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, monoglyceride stearate, lactose, etc. Lubricants include purified talc, stearates, borax, polyethylene glycol, etc. Flavoring agents include sucrose, orange peel, citric acid, tartaric acid, etc.

When preparing oral liquid preparations, flavoring agents, buffers, stabilizers, odorants, etc. can be added to compound (1), its salt, or a solvate of the present invention to produce oral liquid preparations, syrups, elixirs, etc. in a conventional manner. Flavoring agents may be those listed above, buffers such as sodium citrate, and stabilizers such as tragacanth, gum arabic, and gelatin.

When preparing injections, subcutaneous, intramuscular, and intravenous injections can be prepared by adding a pH adjuster, buffer, stabilizer, isotonicity agent, local anesthetic, etc. to compound (1), its salt, or solvate of the present invention, and using standard methods. pH adjusters and buffers include sodium citrate, sodium acetate, and sodium phosphate. Stabilizers include sodium pyrosulfite, sodium edetate, thioglycolic acid, and thiolactic acid. Local anesthetics include procaine hydrochloride and lidocaine hydrochloride. Isotonicity agents include sodium chloride and glucose.

When preparing suppositories, known suppository carriers, such as polyethylene glycol, lanolin, cocoa butter, fatty acid triglycerides, etc., and, if necessary, surfactants such as Tween (registered trademark), can be added to compound (1), a salt thereof, or a solvate thereof of the present invention, and then the suppositories can be prepared by conventional methods.

When the pharmaceutical composition of the present invention is used as a pharmaceutical composition for treating malignant tumors, the dosage will vary depending on the patient's body weight, age, sex, symptoms, dosage form, and number of administrations, etc., but typically, for an adult, the daily dose of compound (1) of the present invention is in the range of 10 μg to 500 mg, preferably 1 mg to 300 mg.
The administration frequency can be divided into one or two injections every day to two weeks.

The present invention will now be explained in more detail using examples, but the present invention is not limited to these examples in any way.

Example 1
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 1)

(1) 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1-1)
To a solution of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (2.10 g, 11.1 mmol) in N,N-dimethylformamide (55 mL) were added potassium carbonate (2.30 g, 16.7 mmol) and iodomethane (0.837 mL, 13.4 mmol) under ice cooling, and the mixture was stirred for 1 hour. Water (200 mL) was added to the reaction solution, and the precipitated solid was collected by filtration and dried to obtain the title compound (1-1) (2.11 g, 10.4 mmol, yield 94%).
¹ H-NMR (CDCl ₃ ) δ: 3.85 (3H, s), 6.59 (1H, d, J=3.7Hz), 7.18 (1H, d, J=3.7Hz).

(2) 2-chloro-7-methyl-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1-2)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 1-1) (172 mg, 0.851 mmol) in dioxane (8.5 mL), phenylboronic acid (124 mg, 1.02 mmol), potassium carbonate (176 mg, 1.27 mmol), water (2 mL), and bis(triphenylphosphine)palladium(II) dichloride (5.00 mg, 7.12 μmol) were added, and the mixture was stirred at 110°C for 2 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (1-2) (50.0 mg, 0.205 mmol, yield 24%) was obtained from the n-hexane:ethyl acetate (4:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.90 (3H, s), 6.82 (1H, d, J = 3.7Hz), 7.23 (1H, d, J = 3.7Hz), 7.53-7.55 (3H, m), 8.10-8.12 (2H, m).

(3) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1-3)
To a solution of 2-chloro-7-methyl-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1-2) (50.0 mg, 0.205 mmol) in dioxane (2 mL), benzimidazole (29.0 mg, 0.246 mmol), cesium carbonate (10 mg, 0.308 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (9.60 mg, 20.1 μmol), and tris(dibenzylideneacetone)dipalladium (19.0 mg, 20.1 μmol) were added, and the mixture was stirred under reflux for 3 hours. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography, and the title compound (1-3) (16.0 mg, 49.2 μmol, yield 24%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.99 (3H, s), 6.86 (1H, d, J = 3.7Hz), 7.30 (1H, d, J = 3.7Hz), 7.37 (1H, ddd, J = 0.9Hz, 8.2Hz, 8.2Hz), 7.44 (1H, ddd, 0 9Hz, 8.2Hz, 8.2Hz), 7.57-7.63 (3H, m), 7.87 (1H, d, J = 8.2Hz), 8.23-8.26 (2H, m), 8.81 (1H, d, J = 8.2Hz), 9.29 (1H, s).

(4) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 1)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1-3) (16.0 mg, 49.2 μmol) in methanol (2 mL) was added 4 M hydrochloric acid/dioxane solution (0.2 mL), and the mixture was stirred at room temperature for 10 minutes. After the solvent was evaporated under reduced pressure, ethyl acetate was added to the residue, and the resulting solid was collected by filtration and dried to obtain the title compound (1) (7.50 mg).
^1H -NMR (DMSO- _d6 ) δ: 3.99 (3H, s), 7.06 (1H, d, J = 3.7Hz), 7.44 (1H, dd, J = 7.3Hz, 8.0Hz), 7.54 (1H, dd, J = 7.3Hz, 8.3Hz), 7.64-7. 70 (3H, m), 7.77 (1H, d, J = 3.7Hz), 7.84 (1H, d, J = 8.0Hz), 8.35-8.38 (2H, m), 8.83 (1H, d, J = 8.3Hz), 9.58 (1H, s).

Compounds (40) and (45) were synthesized from compound (1-1) according to the synthesis method of compound (1).
5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluoroaniline hydrochloride (Compound 40)
^1H -NMR ( _CD3 OD) δ: 4.07 (3H, s), 7.13 (1H, d, J = 3.8Hz), 7.49-7.57 (1H, m), 7.75 (1H, d, J = 3.8Hz), 7.75-7.90 (2H, m ), 7.97 (1H, d, J = 8.7Hz), 8.22-8.28 (1H, m), 8.31-8.37 (1H, m), 9.14 (1H, d, J = 8.2Hz), 10.54 (1H, s).

2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 45)
^1H -NMR ( _CD3 OD) δ: 4.02 (3H, s), 4.06 (3H, s), 7.09 (1H, d, J = 3.7Hz), 7.61 (1H, d, J = 3.7Hz), 7.74-7.80 (1H, m), 7.8 2-7.88 (1H, m), 7.95 (1H, d, J = 8.2Hz), 8.49 (1H, s), 8.72 (1H, s), 9.14 (1H, d, J = 8.2Hz), 10.55 (1H, s).

Example 2
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 41)

(1) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 41-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 19-1) (67.4 mg, 0.257 mmol) in dioxane (2.6 mL), benzimidazole (36.5 mg, 0.309 mmol), cesium carbonate (126 mg, 0.385 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (12.3 mg, 20.0 μmol), and tris(dibenzylideneacetone)dipalladium (4.70 mg, 5.10 μmol) were added, and the mixture was heated at 180°C for 8 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (41-1) (56.8 mg, 0.165 mmol, yield 64%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.00 (3H, s), 6.84 (1H, d, J = 3.7Hz), 7.25-7.36 (3H, m), 7.37-7.50 (2H, m), 7.90 (1H, d, J = 7.8Hz), 8.24-8.32 (2H, m), 8.81 (1H, d, J = 8.2Hz), 9.30 (1H, s).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 41)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 41-1) (56.0 mg, 0.163 mmol) in methanol (3 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (41) (45.4 mg).
^1H -NMR ( _CD3 OD) δ: 4.05 (3H, s), 7.08 (1H, d, J = 3.7Hz), 7.35-7.43 (2H, m), 7.69 (1H, d, J = 3.7Hz), 7.71-7 .85 (2H, m), 7.94 (1H, d, J = 8.2Hz), 8.38-8.45 (2H, m), 9.11 (1H, d, J = 8.2Hz), 10.46 (1H, s).

Example 3
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 44)

(1) 2-chloro-4-(1H-imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 44-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 1-1) (83.7 mg, 0.414 mmol) in N,N-dimethylformamide (2 mL), sodium hydride (60% oil dispersion) (30.0 mg, 0.621 mmol) and imidazole (31.0 mg, 0.455 mmol) were added under ice cooling, and the mixture was stirred for 20 minutes. Water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was then evaporated under reduced pressure to obtain the title compound (44-1) (109 mg) as a crude product.

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 44-2)
A solution of 2-chloro-4-(1H-imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 44-1) (107 mg) in dioxane (4.6 mL) was placed in a sealed reaction vessel, and benzimidazole (65.0 mg, 0.550 mmol), cesium carbonate (224 mg, 0.687 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (23.5 mg, 50.0 μmol), and tris(dibenzylideneacetone)dipalladium (8.40 mg, 9.20 μmol) were added, followed by heating at 120°C for 14 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and from the dichloromethane:methanol (70:1) fraction, the title compound (44-2) (21.4 mg, 67.9 μmol, two-step yield 16%) was obtained.
^1H -NMR (DMSO- _d6 ) δ: 3,98 (3H, s), 7.19 (1H, d, J = 3.7Hz), 7.30 (1H, s), 7.36-7.42 (1H, m), 7.46-7.53 (1H, m), 7.76 (1H, d , J=3.7Hz), 7.81 (1H, d, J=7.8Hz), 8.38-8.42 (1H, m), 8.73 (1H, d, J=7.8Hz), 9.02 (1H, s), 9.48 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 44)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 44-2) (20.3 mg, 64.4 μmol) in methanol (4 mL), 4 M hydrochloric acid/dioxane solution (0.4 mL) was added and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to give the title compound (44) (14.4 mg).
^1H -NMR ( _CD3 OD) δ: 4.15 (3H, s), 7.25 (1H, d, J = 3.7Hz), 7.71-7.78 (1H, m), 7.80-7.86 (1H, m), 7.92 (1H, d, J = 3.7H z), 7.95 (1H, s), 7.96-8.00 (1H, m), 8.78 (1H, s), 9.05 (1H, d, J=8.7Hz), 10.21 (1H, s), 10.47 (1H, s).

Example 4
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(5-fluoropyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 49)

(1) 2-chloro-4-(5-fluoropyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 49-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 1-1) (145 mg, 0.718 mmol) in dioxane (7 mL), (5-fluoropyridin-3-yl)boronic acid (111 mg, 0.790 mmol), potassium carbonate (149 mg, 1.08 mmol), water (1 mL), and bis(triphenylphosphine)palladium(II) dichloride (10.0 mg, 14.0 μmol) were added, and the mixture was heated at 110° C. for 1 hour. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under reduced pressure to obtain the title compound (49-1) (117 mg) as a crude product.

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(5-fluoropyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 49-2)
A solution of 2-chloro-4-(5-fluoropyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 49-1) (177 mg) in dioxane (7 mL) was placed in a sealed reaction vessel, and benzimidazole (96.0 mg, 0.810 mmol), tripotassium phosphate (286 mg, 1.35 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (32.5 mg, 67.5 μmol), and tris(dibenzylideneacetone)dipalladium (18.5 mg, 20.3 μmol) were added, followed by heating at 120°C for 4 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (49-2) (5.00 mg, 14.5 μmol, two-step yield 2%) was obtained from the dichloromethane:methanol (20:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.05 (3H, s), 6.86 (1H, d, J = 3.7Hz), 7.33 (1H, d, J = 3.7Hz), 7.33-7.44 (1H, m), 7.45-7.50 (1H, m), 7.89 (1H, d, J = 7.8Hz), 8.26-8.32 (1H, m), 8.68 (1H, d, J = 2.8Hz), 8.75 (1H, d, J = 7.8Hz), 9.26 (1H, s), 9.28-9.32 (1H, m).

(3) 2-(1H-benzo[d]imidazol-1-yl)-4-(5-fluoropyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 49)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(5-fluoropyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 49-2) (5.00 mg, 14.5 μmol) in methanol (3 mL), 4 M hydrochloric acid/dioxane solution (0.2 mL) was added and the mixture was stirred at room temperature for 15 minutes. After evaporating the solvent under reduced pressure, ethyl acetate was added to the residue, and the resulting solid was collected by filtration and dried to obtain the title compound (49) (4.7 mg).
^1H -NMR ( _CD3 OD) δ: 4.12 (3H, s), 7.17-7.22 (1H, m), 7.75-7.90 (3H, m), 7.94-8.02 (1H, m), 8.78- 8.84 (1H, m), 8.87 (1H, s), 9.10-9.16 (1H, m), 9.47 (1H, s), 10.67 (1H, d, J=4.4Hz).

Example 5
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(1H-pyrrol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 8)

(1) 2-chloro-7-methyl-4-(1H-pyrrol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 8-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 1-1) (120 mg, 0.594 mmol) in N,N-dimethylformamide (8 mL), pyrrole (60.0 mg, 0.909 mmol) and sodium hydride (60% oil dispersion) (50.0 mg, 1.25 mmol) were added under ice-cooling, and the mixture was stirred for 1 hour. Water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (8-1) (129 mg, 0.554 mmol, yield 93%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.87 (3H, s), 6.43 (2H, dd, J = 2.3Hz, 2.3Hz), 6.74 (1H, d, J = 3.7Hz), 7.18 (1H, d, J = 3.7Hz), 7.74 (2H, dd, J = 2.3Hz, 2.3Hz).

(2) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(1H-pyrrol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 8-2)
To a solution of 2-chloro-7-methyl-4-(1H-pyrrol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 8-1) (137 mg, 0.590 mmol) in toluene (5 mL), benzimidazole (83.0 mg, 0.708 mmol), tripotassium phosphate hydrate (271 mg, 1.18 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (28.4 mg, 59.0 μmol), and tris(dibenzylideneacetone)dipalladium (54.0 mg, 59.0 μmol) were added, and the mixture was stirred at 110°C for 3 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (8-2) (162 mg, 0.515 mmol, yield 87%) was obtained from the n-hexane:ethyl acetate (1:2) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.96 (3H, s), 6.49 (2H, dd, J=2.3Hz, 2.3Hz), 6.77 (1H, d, J=3. 7Hz), 7.19 (1H, d, J = 3.2Hz), 7.38 (1H, ddd, J = 1.4Hz, 7.8Hz, 7.8Hz ), 7.45 (1H, ddd, J = 1.4Hz, 7.8Hz, 7.8Hz), 7.84 (2H, dd, J = 2.3Hz, 2 .3Hz), 7.87 (1H, d, J = 7.8Hz), 8.71 (1H, d, J = 7.8Hz), 9.18 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(1H-pyrrol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 8)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(1H-pyrrol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 8-2) (162 mg, 0.515 mmol) in methanol (4 mL), 4 M hydrochloric acid/dioxane solution (0.8 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (8) (156 mg).
^1H -NMR (DMSO- _d6 ) δ: 3.97 (3H, s), 6.61 (2H, dd, J = 2.4Hz, 3.1Hz), 7.14 (1H, d, J = 3.7Hz), 7.49 (1H, dd, J = 7.6Hz, 7.9Hz), 7.59 (1H, dd, J = 7.6H z, 8.3Hz), 7.73 (1H, d, J = 3.7Hz), 7.86 (1H, d, J = 7.9Hz), 8.11 (2H, dd, J=2.4Hz, 3.1Hz), 8.80 (1H, d, J=8.3Hz), 9.83 (1H, s).

Example 6
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(pyrimidin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 9)

(1) 2-chloro-7-methyl-4-(pyrimidin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 9-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 1-1) (320 mg, 1.58 mmol) in dioxane (15 mL), pyrimidine-5-boronic acid (215 mg, 1.74 mmol), 1 M aqueous sodium carbonate solution (3.00 mL, 3.00 mmol), and bis(triphenylphosphine)palladium(II) dichloride (111 mg, 0.158 mmol) were added, and the mixture was stirred at 140°C for 1 hour. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in diethyl ether, filtered, and dried to obtain the title compound (9-1) (202 mg) as a crude product.

(2) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(pyrimidin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 9-2)
To a solution of 2-chloro-7-methyl-4-(pyrimidin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 9-1) (202 mg) in toluene (5 mL), benzimidazole (145 mg, 1.23 mmol), tripotassium phosphate hydrate (379 mg, 1.64 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (39.6 mg, 82.4 μmol), and tris(dibenzylideneacetone)dipalladium (74.5 mg, 82.4 μmol) were added, and the mixture was stirred at 110°C for 1 hour. After cooling, water and n-hexane were added to the reaction solution, and the precipitated solid was collected by filtration. The solid was dissolved in a mixture of chloroform and methanol, filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in chloroform, filtered, and dried to obtain the title compound (9-2) (231 mg, 0.706 mmol, two-step yield 45%).
^1H -NMR (DMSO- _d6 ) δ: 3.95 (3H, s), 7.13 (1H, d, J = 3.7Hz), 7.40 (1H, ddd, J = 0.9Hz, 7.8Hz, 7.8Hz), 7.50 (1H, ddd, J = 0.9Hz, 7.8Hz, 8.2Hz), 7 .78 (1H, d, J = 3.7Hz), 7.80 (1H, d, J = 7.8Hz), 8.76 (1H, d, J = 8.2Hz), 9.36 (1H, s), 9.57 (1H, s), 9.64 (1H, s), 9.67 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(pyrimidin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 9)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(pyrimidin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 9-2) (231 mg, 0.706 mmol) in methanol (8 mL), 4 M hydrochloric acid/dioxane solution (1 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (9) (208 mg).
^1H -NMR (DMSO- _d6 ) δ: 3.98 (3H, s), 7.14 (1H, d, J = 3.7Hz), 7.41 (1H, ddd, J = 0.9Hz, 7.8Hz, 7.8Hz), 7.51 (1H, ddd, J = 0.9Hz, 7.8Hz, 8.2Hz), 7 .78 (1H, d, J = 3.7Hz), 7.80 (1H, d, J = 7.8Hz), 8.76 (1H, d, J = 8.2Hz), 9.39 (1H, s), 9.59 (1H, s), 9.68 (1H, s), 9.88 (1H, s).

Compounds (10), (11), (87), (88), and (89) were synthesized from compound (1-1) according to the synthesis method of compound (9).
2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(pyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 10)
^1H -NMR ( _CD3 OD) δ: 4.12 (3H, s), 7.29 (1H, d, J = 3.7Hz), 7.77 (1H, ddd, J = 0.9 Hz, 7.3Hz, 8.2Hz), 7.85 (1H, ddd, J=0.9Hz, 7.3Hz, 8.2Hz), 7.9 6 (1H, d, J = 3.7Hz), 7.97 (1H, d, J = 8.2Hz), 9.04 (2H, d, J = 6.9Hz), 9.12 (1H, d, J = 8.2Hz), 9.14 (2H, d, J = 6.9Hz), 10.66 (1H, s).

2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 11)
^1H -NMR ( _CD3 OD) δ: 3.24 (3H, s), 7.26 (1H, d, J = 3.7Hz), 7.77 (1H, dd, J = 7.3Hz, 7.8Hz), 7.84 (1H, dd, J=7.8Hz, 8.2Hz), 7.89 (1H, d, J=3.7Hz), 7.97 (1H, d, J=8.2Hz), 8.34 ( 1H, dd, J=6.0Hz, 8.2Hz), 9.07 (1H, dd, J=1.8Hz, 6.0Hz), 9.11 (1H, d, J=7.3Hz) , 9.56 (1H, ddd, J=1.8Hz, 1.8Hz, 8.2Hz), 9.86 (1H, d, J=1.8Hz), 10.67 (1H, s).

2-(1H-benzo[d]imidazol-1-yl)-4-(furan-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 87)
^1H -NMR ( _CD3 OD) δ: 3.93 (3H, s), 6.99 (1H, d, J = 3.6Hz), 7.34 (1H, dd, J = 0.8Hz, 2.0Hz), 7.58 (1H, d, J = 3.6Hz) , 7.71-7.82 (3H, m), 7.90-7.93 (1H, m), 8.63-8.64 (1H, m), 9.03 (1H, d, J=8.0Hz), 10.41 (1H, s).

2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 88)
^1H -NMR ( _CD3 OD) δ: 3.96 (3H, s), 7.06 (1H, d, J = 3.6Hz), 7.58 (1H, d, J = 3.6Hz), 7.64 (1H, dd, J = 3.2Hz, 5.2Hz), 7.70-7.81 (2H, m), 7.89-7.93 (1H, m), 8.04 (1H, dd, J = 1.2Hz, 5.2Hz), 8.55 (1H, dd, J = 1.6Hz, 3.2Hz), 9.00-9.03 (1H, m), 10.38 (1H, s).

7-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3-dihydro-1,4-dioxino[2,3-b]pyridine hydrochloride (Compound 89)
^1H -NMR ( _CD3 OD) δ: 4.05 (3H, s), 4.48-4.51 (2H, m), 4.69-4.73 (2H, m), 7.07 (1H, d, J=3.6Hz), 7. 73 (1H, d, J = 3.6Hz), 7.75-7.86 (2H, m), 7.96 (1H, d, J = 8.0Hz), 8.43 (1H, s), 8.77 (1H s), 9.04 (1H, d, J=8.0Hz), 10.59 (1H, s).

Example 7
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(6-methylpyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 17)

(1) 2-chloro-7-methyl-4-(6-methylpyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 17-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 1-1) (150 mg, 0.742 mmol) in dioxane (3.7 mL), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (170 mg, 0.779 mmol), 1 M aqueous sodium carbonate solution (1.00 mL, 1.00 mmol), and bis(triphenylphosphine)palladium(II) dichloride (52.1 mg, 74.2 μmol) were added, and the mixture was heated at 140° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The solid was suspended in diethyl ether, collected by filtration, and dried to obtain the title compound (17-1) (132 mg) as a crude product.

(2) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(6-methylpyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 17-2)
To a solution of 2-chloro-7-methyl-4-(6-methylpyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 17-1) (132 mg) in dioxane (5 mL), benzimidazole (72.0 mg, 0.613 mmol), cesium carbonate (249 mg, 0.767 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (48.0 mg, 101 μmol), and tris(dibenzylideneacetone)dipalladium (46.0 mg, 51.0 μmol) were added, and the mixture was heated at 170°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The solid was purified by silica gel column chromatography (amino silica gel), and the title compound (17-2) (70.0 mg, 0.205 mmol, two-step yield 28%) was obtained from the n-hexane:ethyl acetate (1:3) fraction.
^1H -NMR ( _CD3 OD) δ: 2.97 (3H, s), 4.10 (3H, s), 7.24 (1H, d, J = 3.7Hz), 7.77 (1H, dd, J=7.6Hz, 8.2Hz), 7.85 (1H, dd, J=7.6Hz, 8.9Hz), 7.89 (1H, d, J=3.7Hz) ), 7.99 (1H, d, J = 8.2Hz), 8.20 (1H, d, J = 8.2Hz), 9.10 (1H, d, J = 8.9Hz) , 9.40 (1H, dd, J=1.8Hz, 8.2Hz), 9.66 (1H, d, J=1.8Hz), 10.23 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(6-methylpyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 17)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(6-methylpyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 17-2) (70.0 mg, 0.205 mmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and stirred for 15 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (17) (77.0 mg).
^1H -NMR ( _CD3 OD) δ: 2.99 (3H, s), 4.13 (3H, s), 7.26 (1H, d, J = 3.7Hz), 7.79 (1H, dd, J=7.6Hz, 8.2Hz), 7.86 (1H, dd, J=7.6Hz, 8.9Hz), 7.89 (1H, d, J=3.7Hz ), 7.99 (1H, d, J = 8.2Hz), 8.21 (1H, d, J = 8.2Hz), 9.12 (1H, d, J = 8.9Hz) , 9.44 (1H, dd, J=1.8Hz, 8.2Hz), 9.69 (1H, d, J=1.8Hz), 10.67 (1H, s).

Example 8
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(2-methylpyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 18)

(1) 2-chloro-7-methyl-4-(2-methylpyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 18-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1-1) (150 mg, 0.742 mmol) in dioxane (3.7 mL), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (170 mg, 0.779 mmol), 1 M aqueous sodium carbonate solution (1.00 mL, 1.00 mmol), and bis(triphenylphosphine)palladium(II) dichloride (52.1 mg, 74.2 μmol) were added, and the mixture was heated at 140°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in ethyl acetate, filtered, and dried to give the title compound (18-1) (80.0 mg) as a crude product.

(2) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(2-methylpyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 18-2)
To a solution of 2-chloro-7-methyl-4-(2-methylpyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 18-1) (80.0 mg) in N,N-dimethylformamide (3.1 mL), benzimidazole (44.0 mg, 0.372 mmol), cesium carbonate (151 mg, 0.465 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (29.0 mg, 60.9 μmol), and tris(dibenzylideneacetone)dipalladium (28.0 mg, 30.6 μmol) were added, and the mixture was heated at 160°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (18-2) (80.0 mg, 0.235 mmol, two-step yield 32%) was obtained from the n-hexane:ethyl acetate (1:2) fraction.
^1H -NMR (DMSO- _d6 ) δ: 3.01 (3H, s), 4.11 (3H, s), 7.30 (1H, d, J = 3.7Hz), 7.75 (1H, ddd, J = 0.9Hz, 7.3Hz, 7.8Hz), 7.84 (1H, ddd, J = 0.9Hz, 7.3Hz, 8.2Hz), 7.96 (1H, d, J = 3.7Hz) , 7.98 (1H, dd, J = 0.9Hz, 7.8Hz), 8.83 (1H, dd, J = 1.0Hz, 5.5Hz), 8.89 (1H, d, J = 1.0Hz), 8.97 (1H, d, J = 5.5Hz), 9.10 (1H, dd, J = 0.9Hz, 8.2Hz), 9.55 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(2-methylpyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 18)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-4-(2-methylpyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 18-2) (80.0 mg, 0.235 mmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (18) (94.5 mg).
^1H -NMR (DMSO- _d6 ) δ: 3.01 (3H, s), 4.15 (3H, s), 7.32 (1H, d, J = 3.7Hz), 7.79 (1H, ddd, J = 0.9Hz, 7.3Hz, 7.8Hz), 7.87 (1H, ddd, J=0.9Hz, 7.3Hz, 8.2Hz), 7.96 (1H, d, J=3.7Hz) , 8.00 (1H, dd, J = 0.9Hz, 7.8Hz), 8.83 (1H, dd, J = 1.0Hz, 5.5Hz), 8.89 (1H, d, J = 1.0Hz), 8.97 (1H, d, J = 5.5Hz), 9.12 (1H, dd, J = 0.9Hz, 8.2Hz), 9.60 (1H, s).

Example 9
Synthesis of 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol hydrochloride (Compound 26)

(1) 4-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol (Compound 26-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 1-1) (304 mg, 1.50 mmol) in N,N-dimethylformamide (15 mL), 4-hydroxyphenylboronic acid (211 mg, 1.53 mmol), potassium carbonate (312 mg, 2.25 mmol), water (3 mL), and tetrakis(triphenylphosphine)palladium (86.0 mg, 74.4 μmol) were added, and the mixture was stirred at 90°C for 1 hour. After cooling, water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (26-1) (295 mg, 1.14 mmol, 76% yield) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 3.82 (3H, s), 6.95 (2H, d, J = 8.7Hz), 6.97 (1H, d, J = 3.7Hz), 7.66 (1H, d, 3.7Hz), 8.07 (2H, d, J = 8.7Hz), 10.16 (1H, brs).

(2) 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol (Compound 26-2)
To a solution of 4-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol (Compound 26-1) (252 mg, 0.970 mmol) in N,N-dimethylformamide (5 mL), benzimidazole (126 mg, 1.06 mmol), cesium carbonate (411 mg, 1.26 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (46.2 mg, 97.0 μmol), and tris(dibenzylideneacetone)dipalladium (88.8 mg, 97.0 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The solid was dissolved in chloroform and then filtered through Celite. The filtrate was concentrated under reduced pressure. The residue was suspended in methanol, filtered, and dried to obtain the title compound (26-2) (160 mg, 0.468 mmol, yield 48%).
^1H -NMR (DMSO- _d6 ) δ: 3.95 (3H, s), 7.02 (1H, d, J = 3.7Hz), 7.03 (2H, d, J = 6.9Hz), 7.38 (1H, dd, J = 7.3Hz, 7.8Hz), 7.48 (1H, dd, J = 7.3Hz, 7.8Hz) ), 7.67 (1H, d, J = 3.7Hz), 7.81 (1H, d, J = 7.8Hz), 8.27 (2H, d, J = 6.9Hz), 8.78 (1H, d, J = 7.8Hz), 9.34 (1H, s), 10.21 (1H, brs).

(3) 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol hydrochloride (Compound 26)
To a suspension of 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol (compound 26-2) (45.0 mg, 0.132 mmol) in methanol (3 mL), a 4 M hydrochloric acid/dioxane solution (0.6 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (26) (40.0 mg).
^1H -NMR (DMSO- _d6 ) δ: 3.96 (3H, s), 7.02 (1H, d, J = 3.7Hz), 7.03 (2H, d, J = 6.9Hz), 7.42 (1H, dd, J = 7.3Hz, 7.8Hz), 7.48 (1H, dd, J = 7.3Hz, 7.8Hz) ), 7.70 (1H, d, J = 3.7Hz), 7.83 (1H, d, J = 7.8Hz), 8.27 (2H, d, J = 6.9Hz), 8.81 (1H, d, J = 7.8Hz), 9.52 (1H, s), 10.20 (1H, brs).

Example 10
Synthesis of 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-methylaniline hydrochloride (Compound 7)

(1) 4-(benzyloxy)-2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 7-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 1-1) (7.24 g, 35.8 mmol) in N,N-dimethylformamide (300 mL), benzyl alcohol (4.47 mL, 43.0 mmol) and sodium hydride (60% oil dispersion) (2.15 g, 53.7 mmol) were added under ice cooling, and the mixture was stirred for 1 hour. Water was added to the reaction solution, which was then returned to room temperature and extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (7-1) (9.42 g, 34.4 mmol, yield 96%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.81 (3H, s), 5.56 (2H, s), 6.51 (1H, d, J=3.2Hz), 6.95 (1H, d, J=3.2Hz), 7.34-7.41 (3H, m), 7.49-7.51 (2H, m).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(benzyloxy)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 7-2)
To a solution of 4-(benzyloxy)-2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 7-1) (1.56 g, 5.69 mmol) in N,N-dimethylformamide (15 mL), benzimidazole (739 mg, 6.26 mmol), cesium carbonate (2.40 g, 7.40 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (271 mg, 0.569 mmol), and tris(dibenzylideneacetone)dipalladium (260 mg, 0.284 mmol) were added, and the mixture was heated at 160°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (7-2) (822 mg, 2.31 mmol, yield 41%) was obtained from the n-hexane:ethyl acetate (1:2) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.86 (3H, s), 5.74 (2H, s), 6.57 (1H, d, J=3.2Hz), 7.30-7.42 (6H, m), 7. 53-7.56 (2H, m), 7.75 (1H, d, J = 7.8Hz), 8.63 (1H, d, J = 7.8Hz), 9.22 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol (Compound 7-3)
Palladium-activated carbon (Pd 10%) (473 mg, 0.440 mmol) was added to a solution of 2-(1H-benzo[d]imidazol-1-yl)-4-(benzyloxy)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 7-2) (790 mg, 2.20 mmol) in chloroform (15 mL) and methanol (15 mL), and the mixture was stirred under a hydrogen atmosphere for 4 hours. The reaction solution was filtered through Celite, and the solvent was evaporated under reduced pressure. The residue was suspended in n-hexane and ethyl acetate, then filtered and dried to obtain the title compound (7-3) (581 mg, 2.19 mmol, yield 99%).
^1H -NMR (DMSO- _d6 ) δ: 3.83 (3H, s), 4.01 (1H, brs), 6.58 (1H, d, J = 3.2Hz), 7.29 (1H, brs), 7.42 (1H, dd, J = 7.2Hz, 8.0Hz), 7.49 (1H, dd, J=7.2Hz, 8.0Hz), 7.80 (1H, d, J=8.4Hz), 8.62 (1H, brs), 9.20 (1H, brs).

(4) 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (Compound 7-4)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol (compound 7-3) (323 mg, 1.22 mmol) in N,N-dimethylformamide (10 mL), triethylamine (0.255 mL, 1.83 mmol) and p-toluenesulfonyl chloride (279 mg, 1.46 mmol) were added and stirred at room temperature for 1 hour. The reaction solution was poured into ice water, and the precipitated solid was collected by filtration and dried to obtain the title compound (7-4) (376 mg, 0.896 mmol, yield 73%).
^1H -NMR (DMSO- _d6 ) δ: 2.45 (3H, s), 3.94 (3H, s), 6.67 (1H, d, J = 3.7Hz), 7.35-7.41 (2H, m), 7.55 (2H, d, J = 7.8Hz), 7 .71 (1H, d, J = 3.7Hz), 7.75-7.80 (1H, m), 8.03 (2H, d, J = 8.2Hz), 8.32-8.37 (1H, m), 8.77 (1H, s).

(5) tert-butyl (3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)(methyl)carbamate (Compound 7-5)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (Compound 7-4) (56.0 mg, 0.133 mmol) in tetrahydrofuran (2 mL), (3-{[(tert-butoxy)carbonyl](methyl)amino}phenyl)boronic acid (50.0 mg, 0.200 mmol), tripotassium phosphate hydrate (76.0 mg, 0.334 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (6.34 mg, 13.3 μmol), and tris(dibenzylideneacetone)dipalladium (12.2 mg, 13.3 μmol) were added and the mixture was stirred at 80°C for 2 hours. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (7-5) (14.0 mg, 30.8 μmol, yield 23%) from the n-hexane:ethyl acetate (1:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 1.55 (9H, s), 2.92 (3H, s), 3.99 (3H, s), 7.11 (1H, d, J=3.7Hz), 7.14 (1H, s), 7.41-7. 64 (3H, m), 7.81 (1H, d, J = 3.7Hz), 7.83-7.97 (3H, m), 8.89 (1H, d, J = 8.2Hz), 9.70 (1H, s).

(6) 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-methylaniline hydrochloride (Compound 7)
To a suspension of tert-butyl (3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)(methyl)carbamate (compound 7-5) (14.0 mg, 30.8 μmol) in methanol (4 mL) was added 4 M hydrochloric acid/dioxane solution (1 mL), and the mixture was stirred at 60° C. for 20 minutes. After allowing to cool, the solvent was evaporated under reduced pressure. Dichloromethane was added to the residue, and the resulting solid was collected by filtration and dried to obtain the title compound (7) (6.60 mg).
^1H -NMR (DMSO- _d6 ) δ: 2.91 (3H, s), 3.99 (3H, s), 7.09 (1H, d, J = 3.7Hz), 7.12 (1H, s), 7.43-7.61 (3H, m), 7.81 (1H, d, J = 3.7Hz), 7.82-7.96 (3H, m), 8.88 (1H, d, J = 8.2Hz), 9.75 (1H, s).

Example 11
Synthesis of 5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluoro-N-methylaniline hydrochloride (Compound 46)

(1) tert-butyl (5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluorophenyl)(methyl)carbamate (Compound 46-1)
A solution of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (compound 7-4) (129 mg, 0.307 mmol) in tetrahydrofuran (2 mL) was placed in a sealed reaction vessel, and tert-butyl N-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-N-methylcarbamate (216 mg, 0.615 mmol), tripotassium phosphate hydrate (211 mg, 0.921 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (7.3 mg, 15.0 μmol), palladium (II) acetate (1.40 mg, 6.14 μmol) was added, and the mixture was heated at 80 ° C. for 3 hours. After cooling, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (46-1) (60.2 mg, 0.127 mmol, yield 41%) was obtained from the dichloromethane:methanol (20:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.25 (9H, s), 3.35 (3H, s), 4.01 (3H, s), 6.84 (1H, d, J = 3.2Hz), 7.28-7.30 (1H, m), 7.30- 7.50 (3H, m), 7.90 (1H, d, J = 8.2Hz), 8.12-8.22 (2H, m), 8.80 (1H, d, J = 7.8Hz), 9.29 (1H, s).

(2) 5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluoro-N-methylaniline hydrochloride (Compound 46)
To a suspension of tert-butyl (5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluorophenyl)(methyl)carbamate (Compound 46-1) (59.0 mg, 0.125 mmol) in methanol (3 mL) was added 4 M hydrochloric acid/dioxane solution (0.6 mL), and the mixture was stirred at 40° C. for 1 hour. After allowing to cool, the solvent was evaporated under reduced pressure. Ethyl acetate was added to the residue, and the resulting solid was collected by filtration and dried to obtain the title compound (46) (32.8 mg).
^1H -NMR ( _CD3 OD) δ: 3.02 (3H, s), 4.06 (3H, s), 7.08-7.13 (1H, m), 7.36-7.44 (1H, m), 7.69-7.73 (1H, m), 7.74-7.80 (1 H, m), 7.80-7.88 (1H, m), 7.94-8.00 (2H, m), 8.02 (1H, d, J = 8.0Hz), 9.16 (1H, d, J = 8.2Hz), 10.54 (1H, s).

Example 12
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 48)

(1) 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 48-1)
A solution of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (Compound 7-4) (59.7 mg, 0.142 mmol) in tetrahydrofuran (1.6 mL) was placed in a sealed reaction vessel, and (2,3-dihydro-1,4-benzodioxin-6-yl)boronic acid (51.3 mg, 0.284 mmol), tripotassium phosphate hydrate (98.7 mg, 0.430 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (3.4 mg, 7.10 μmol), and palladium(II) acetate (0.630 mg, 2.84 μmol) were added, followed by heating at 80°C for 1 hour. After allowing to cool, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (48-1) (54.4 mg, 0.142 mmol, yield 100%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.98 (3H, s), 4.38 (4H, s), 6.84-6.90 (1H, m), 7.09 (1H, d, J = 8.2Hz), 7.22 (1H, d, J = 3.6Hz), 7.34-7 .50 (2H, m), 7.78-7.86 (1H, m), 7.82 (1H, s), 7.88 (1H, d, J = 8.4Hz), 8.82 (1H, d, J = 8.4Hz), 9.30 (1H, s).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 48)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 48-1) (56.2 mg, 0.146 mmol) in methanol (6 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to give the title compound (48) (32.5 mg).
^1H -NMR ( _CD3 OD) δ: 4.01 (3H, s), 4.36 (4H, s), 7.01 (1H, d, J = 3.7Hz), 7.07 (1H, d, J = 9.2Hz), 7.60 (1H, d, J = 3.7Hz), 7.69 -7.81 (2H, m), 7.82-7.87 (1H, m), 7.83 (1H, s), 7.92 (1H, d, J = 8.2Hz), 9.06 (1H, d, J = 8.7Hz), 10.34 (1H, s).

Compounds (47) and (58) were synthesized from compound (7-4) according to the synthesis method of compound (48).
2-(1H-benzo[d]imidazol-1-yl)-4-(3,4-dimethoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 47)
^1H -NMR ( _CD3 OD) δ: 3.96 (3H, s), 4.00 (3H, s), 4.02 (3H, s), 7.06 (1H, d, J = 3.5Hz), 7.18 (1H, d, J = 8.2Hz), 7.6 3 (1H, d, J = 3.5Hz), 7.71-7.84 (2H, m), 7.90-7.99 (3H, m), 9.01 (1H, d, J = 8.7Hz), 10.38 (1H, s).

3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylaniline hydrochloride (Compound 58)
^1H -NMR ( _CD3 OD) δ: 3.42 (6H, s), 4.09 (3H, s), 7.18 (1H, d, J = 3.7Hz), 7.74-7.80 (1H, m), 7.77 (1H, d, J = 3.7Hz), 7.82-7 91 (3H, m), 7.97 (1H, d, J = 8.2Hz), 8.44-8.49 (1H, m), 8.65 (1H, s), 9.15 (1H, d, J = 8.2Hz), 10.58 (1H, s).

Example 13
Synthesis of 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol hydrochloride (Compound 27)

(1) 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 27-1)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[23-d]pyrimidin-4-yl 4-methylbenzenesulfonate (compound 7-4) (317 mg, 0.756 mmol) in dimethoxyethane (8 mL), 3-methoxyphenylboronic acid (172 mg, 1.13 mmol), potassium carbonate (135 mg, 0.983 mmol), water (1.6 mL), and tetrakis(triphenylphosphine)palladium (87.0 mg, 75.3 μmol) were added, and the mixture was heated at 110°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (27-1) (260 mg, 0.731 mmol, yield 97%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.95 (3H, s), 3.98 (3H, s), 6.86 (1H, d, J = 3.7Hz), 7.12 (1H, ddd, J = 0 9Hz, 2.3Hz, 7.8Hz), 7.23 (1H, d, J = 3.7Hz), 7.37 (1H, dd, J = 7.3Hz, 7.8H z), 7.45 (1H, dd, J=7.3Hz, 7.8Hz), 7.51 (1H, dd, J=7.8Hz, 7.8Hz), 7.80- 7.85 (2H, m), 7.87 (1H, d, J = 7.8Hz), 8.82 (1H, d, J = 2.3Hz), 9.28 (1H, s).

(2) 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol (Compound 27-2)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 27-1) (310 mg, 0.872 mmol) in dichloromethane (10 mL), 1 M boron tribromide/dichloromethane solution (6.00 mL, 6.00 mmol) was added and stirred at room temperature for 20 minutes. A saturated aqueous solution of sodium bicarbonate was added to the reaction solution, and the precipitated solid was collected by filtration. The solid was suspended in dichloromethane, collected by filtration, and dried to obtain the title compound (27-2) (100 mg, 0.292 mmol, yield 34%).
^1H -NMR (DMSO- _d6 ) δ: 3.98 (3H, s), 6.99 (1H, d, J = 3.7Hz), 7.03 (1H, dd, J = 0.9Hz, 7.8Hz), 7.45-7.49 (2H, m), 7.57 (1H, dd, J = 7.3Hz, 8.2Hz), 7.77-7.79 (3H, m), 7.85 (1H, d, J = 8.2Hz), 8.84 (1H, d, J = 7.8Hz), 9.60 (1H, s), 9.82 (1H, s).

(3) 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol hydrochloride (Compound 27)
To a suspension of 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenol (compound 27-2) (80.0 mg, 0.234 mmol) in methanol (3 mL), a 4 M hydrochloric acid/dioxane solution (0.5 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (27) (56.2 mg).
^1H -NMR (DMSO- _d6 ) δ: 3.98 (3H, s), 6.99 (1H, d, J = 3.7Hz), 7.05 (1H, dd, J = 0.9Hz, 7.8Hz), 7.46-7.52 (2H, m), 7.59 (1H, dd, J = 7.3Hz, 8.2Hz), 7.77-7.79 (3H, m), 7.86 (1H, d, J = 8.2Hz), 8.86 (1H, d, J = 7.8Hz), 9.75 (1H, s), 9.80 (1H, s).

Example 14
Synthesis of 6-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Compound 100)

(1) tert-butyl 6-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Compound 100-1)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (Compound 7-4) (160 mg, 0.381 mmol) in dimethoxyethane (4 mL), tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (200 mg, 0.557 mmol), potassium carbonate (70.0 mg, 0.506 mmol), water (0.8 mL), and tetrakis(triphenylphosphine)palladium (40.0 mg, 34.6 μmol) were added, and the mixture was heated at 110° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, which was then extracted with chloroform, and the solvent was evaporated under reduced pressure. The residue was purified by preparative TLC (preparative thin layer chromatography), and the title compound (100-1) (160 mg, 0.333 mmol, yield 87%) was obtained from the chloroform:methanol (40:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 1.46 (9H, s), 3.13-3.16 (2H, m), 3.33-3.63 (2H, m), 3.97 (3H, s), 4.70-4.72 (2H, m), 7.08 (1H, d, J = 3 .7Hz), 7.36-7.66 (4H, m), 7.71 (1H, d, J = 3.7Hz), 8.14-8.17 (2H, m), 8.78 (1H, d, J = 8.2Hz), 9.41 (1H, s).

(2) 6-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Compound 100)
A 4M hydrochloric acid/dioxane solution (5 mL) was added to tert-butyl 6-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (compound 100-1) (160 mg, 0.333 mmol), and the mixture was stirred at room temperature for 2 hours. The precipitated solid was collected by filtration, washed with acetone, and then dried to obtain the title compound (100) (133 mg).
^1H -NMR ( _CD3 OD) δ: 3.29-3.37 (2H, m), 3.62 (2H, t, J = 6.4Hz), 4.07 (3H, s), 4.53 (2H, s), 7.11 (1H, d, J = 3.7Hz), 7.51-7.56 (1H, m), 7.71- 7.74 (1H, m), 7.75-7.81 (1H, m), 7.82-7.87 (1H, m), 7.96-8.00 (1H, m), 8.25-8.31 (2H, m), 9.12-9.16 (1H, m), 10.57 (1H, s).

Compound (99) was synthesized from compound (7-4) according to the synthesis method of compound (100).
7-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Compound 99)
^1H -NMR ( _CD3 OD) δ: 3.26-3.32 (2H, m), 3.62 (2H, t, J = 6.4Hz), 4.05 (3H, s), 4.59 (2H, s), 7.12 (1H, d, J = 3.6Hz), 7.52-7.56 (1H, m), 7.70 (1H, d.

Example 15
Synthesis of 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine hydrochloride (Compound 92)

(1) tert-Butyl 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (Compound 92-1)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (Compound 7-4) (100 mg, 0.238 mmol) in dimethoxyethane (2.5 mL), tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carboxylate (128 mg, 0.355 mmol), potassium carbonate (41.0 mg, 0.297 mmol), tetrakis(triphenylphosphine)palladium (32.3 mg, 28.0 μmol), and water (0.5 mL) were added, and the mixture was heated at 110° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (92-1) (91.5 mg, 0.190 mmol, yield 80%) from the dichloromethane:methanol (10:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.47 (9H, s), 3.02 (2H, t, J = 5.8Hz), 3.75 (2H, t, J = 5.8Hz), 3.99 (3 H, s), 4.78 (2H, s), 7.17 (1H, d, J = 3.7Hz), 7.39 (1H, dd, J = 7.6Hz, 7.6Hz ), 7.49 (1H, dd, J = 7.6Hz, 7,6Hz), 7.77 (1H, d, J = 3.7Hz), 7.82 (1H, d, J = 8.2Hz), 8.60 (1H, s), 8.78 (1H, d, J=8.2Hz), 9.33 (1H, s), 9.48 (1H, s).

(2) 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine hydrochloride (Compound 92)
To a suspension of tert-butyl 3-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (Compound 92-1) (90.0 mg, 0.187 mmol) in methanol (5 mL), 4 M hydrochloric acid/dioxane solution (0.6 mL) was added, and the mixture was stirred at room temperature for 2 hours. After cooling, the solvent was evaporated under reduced pressure, and diethyl ether and methanol were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (92) (76.0 mg).
^1H -NMR ( _CD3 OD) δ: 3.51 (2H, t, J = 6.4Hz), 3.78 (2H, t, J = 6.4Hz), 4.12 (3H, s), 4.76 (2H, s), 7.27 (1H, d, J = 3.7Hz), 7.77-7.90 ( 3H, m), 7.99 (1H, d, J = 8.2Hz), 9.02 (1H, d, J = 1.2Hz), 9.14 (1H, d, J = 8.2Hz), 9.62 (1H, d, J = 1.2Hz), 10.69 (1H, s).

Example 16
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 82)

(1) tert-Butyl 5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (Compound 82-1)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (compound 7-4) (156 mg, 0.371 mmol) in dimethoxyethane (4 mL), tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydropyrrolo[2,3-b]pyridine-1-carboxylate (193 mg, 0.557 mmol), potassium carbonate (66.6 mg, 0.482 mmol), water (0.8 mL), and tetrakis(triphenylphosphine)palladium (42.9 mg, 37.1 μmol) were added, and the mixture was heated at 110° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (82-1) (170 mg, 0.364 mmol, yield 98%) from the n-hexane:ethyl acetate (1:2) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.61 (9H, s), 3.24 (2H, t, J=8.6Hz), 3.98 (3H, s), 4.14 (2H, t, J=8.8Hz), 6.84 (1H, d, J=3.6Hz), 7.26 (1H, d, J=3.2Hz), 7.34-7. 42 (1H, m), 7.42-7.50 (1H, m), 7.88 (1H, d, J = 7.6Hz), 8.30-8.37 (1H, m), 8.78 (1H, d, J = 8.0Hz), 9.13 (1H, d, J = 1.6Hz), 9.26 (1H, s).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 82)
To a suspension of tert-butyl 5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (Compound 82-1) (170 mg, 0.382 mmol) in ethanol (8 mL) was added a 4 M hydrochloric acid/dioxane solution (4 mL), and the mixture was heated to reflux for 1 hour. After allowing to cool, the solvent was evaporated under reduced pressure. Ethyl acetate and diethyl ether were added to the residue, and the resulting solid was collected by filtration and dried to obtain the title compound (82) (153 mg).
^1H -NMR ( _CD3 OD) δ: 3.43 (2H, t, J = 8.0Hz), 4.03-4.11 (5H, m), 7.12 (1H, d, J = 4.4Hz), 7.71-7.79 (2H, m), 7.83 (1H, dd , J=7.6Hz, 8.0Hz), 7.96 (1H, d, J=7.6Hz), 8.56-8.65 (2H, m), 9.03-9.12 (1H, m), 10.48-10.61 (1H, m).

Example 17
Synthesis of 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine hydrochloride (Compound 30)

(1) 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine (Compound 30-1)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (compound 7-4) (97.0 mg, 0.231 mmol) in dimethoxyethane (2.5 mL), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (68.0 mg, 0.277 mmol), potassium carbonate (47.0 mg, 0.347 mmol), water (0.5 mL), and tetrakis(triphenylphosphine)palladium (20.0 mg, 17.3 μmol) were added, and the mixture was heated at 110°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (30-1) (85.0 mg, 0.230 mmol, yield 99%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 3.37 (6H, s), 4.01 (3H, s), 7.05 (1H, d, J = 3.7Hz), 7.43 (1H, d d, J=7.5Hz, 7.9Hz), 7.53 (1H, dd, J=7.5Hz, 8.0Hz), 7.66 (1H, d, J=6.0Hz), 7.78 (1H, s), 7.85 (1H, d, J=7.9Hz), 7.90 (1H, d, J=3. 7Hz), 8.21 (1H, d, J = 6.0Hz), 8.76 (1H, d, J = 8.0Hz), 9.35 (1H, s).

(2) 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine hydrochloride (Compound 30)
To a suspension of 4-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine (compound 30-1) (85.0 mg, 0.230 mmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.8 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (30) (97.2 mg).
^1H -NMR (DMSO- _d6 ) δ: 3.37 (6H, s), 4.01 (3H, s), 7.09 (1H, d, J = 3.7Hz), 7.44 (1H, d d, J=7.5Hz, 7.9Hz), 7.53 (1H, dd, J=7.5Hz, 8.0Hz), 7.67 (1H, d, J=6.0Hz), 7.78 (1H, s), 7.85 (1H, d, J=7.9Hz), 7.90 (1H, d, J=3. 7Hz), 8.22 (1H, d, J = 6.0Hz), 8.79 (1H, d, J = 8.0Hz), 9.55 (1H, s).

Compound (31) was synthesized from compound (7-4) according to the synthesis method of compound (30): 5-(2-(1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-3-amine hydrochloride (compound 31).
^1H -NMR (DMSO- _d6 ) δ: 3.16 (6H, s), 4.01 (3H, s), 7.08 (1H, d, J = 3.7Hz), 7.38 (1H, dd, J = 7.3Hz, 7.8Hz), 7.50 (1H, dd, J = 7.3Hz, 7.8Hz), 7.78 (1H, d, J = 3.7Hz) , 7.81 (1H, d, J = 7.8Hz), 7.84 (1H, dd, J = 1.4Hz, 2.8Hz), 8.36 (1H, d, J = 2.8Hz), 8.78 (1H, d, J = 1.4Hz), 8.81 (1H, d, J = 7.8Hz), 9.61 (1H, s).

Example 18
Synthesis of 4-(4-fluorophenyl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 25)

(1) 4-(4-fluorophenyl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 25-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 19-1) (42.0 mg, 0.160 mmol) in N,N-dimethylformamide (2 mL), 4-methyl-1H-benzo[d]imidazole (25.0 mg, 0.192 mmol), cesium carbonate (73.0 mg, 0.224 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (7.62 mg, 16.0 μmol), and tris(dibenzylideneacetone)dipalladium (14.6 mg, 16.0 μmol) were added, and the mixture was heated at 150°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The solid was purified by silica gel column chromatography (amino silica gel), and the title compound (25-1) (42.2 mg, 0.118 mmol, yield 74%) was obtained from the n-hexane:ethyl acetate (1:3) fraction.
^1H -NMR ( _CD3 OD) δ: 2.65 (3H, s), 3.97 (3H, s), 7.01 (1H, d, J = 3.7Hz), 7.32-7.35 (2H, m), 7.50 (1H, d, J = 7.3Hz), 7.61 ( 1H, d, J = 3.7Hz), 7.67 (1H, dd, J = 7.3Hz, 8.7Hz), 8.30-8.39 (2H, m), 8.78 (1H, d, J = 8.7Hz), 10.18 (1H, s).

(2) 4-(4-fluorophenyl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 25)
To a suspension of 4-(4-fluorophenyl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 25-1) (50.0 mg, 0.140 mmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to give the title compound (25) (42.2 mg).
^1H -NMR ( _CD3 OD) δ: 2.71 (3H, s), 4.03 (3H, s), 7.06 (1H, d, J = 3.7Hz), 7.35-7.37 (2H, m), 7.52 (1H, d, J=7.3Hz), 7.65-7.69 (2H, m), 8.34-8.42 (2H, m), 8.90 (1H, d, J=8.7Hz), 10.45 (1H, s).

Example 19
Synthesis of 7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Compound 80)

(1) tert-butyl 7-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Compound 80-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1-1) (155 mg, 0.769 mmol) in dioxane (5 mL), tert-butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (304 mg, 0.846 mmol), potassium carbonate (159 mg, 1.15 mmol), water (0.5 mL), and bis(triphenylphosphine)palladium(II) dichloride (10.8 mg, 15.4 μmol) were added, and the mixture was heated at 140°C for 20 minutes using a microwave synthesizer. After cooling, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (80-1) (258 mg, 0.647 mmol, yield 84%) was obtained from the n-hexane:ethyl acetate (4:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.51 (9H, s), 2.88-3.00 (2H, m), 3.60-3.78 (2H, m), 3.89 (3H, s), 4.65-4.76 (2H, m), 6.80 (1H, d, J = 3.2Hz), 7.21 (1H, d, J = 3.6Hz), 7.31 (1H, d, J = 8.0Hz), 7.85-7.98 (2H, m).

(2) tert-butyl 7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Compound 80-2)
To a solution of tert-butyl 7-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Compound 80-1) (258 mg, 0.647 mmol) in N,N-dimethylformamide (6 mL), 4-methyl-1H-benzo[d]imidazole (103 mg, 0.776 mmol), cesium carbonate (316 mg, 0.971 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (61.5 mg, 0.129 mmol), and tris(dibenzylideneacetone)dipalladium (29.7 mg, 32.4 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography, and the title compound (80-2) (236 mg, 0.476 mmol, yield 74%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.53 (9H, s), 2.75 (3H, s), 2.90-3.04 (2H, m), 3.66-3.80 (2H, m), 3.99 (3H, s), 4.70-4.81 (2H, m), 6.84 (1H, d, J = 3.6Hz), 7.19 (1H, d, J = 6.8Hz), 7.23 (1H, d, J = 3.6Hz), 7.31-7.42 (2H, m), 7.96-8.02 (1H, m), 8.04 (1H, d, J = 8.4Hz), 8.64 (1H, d, J = 8.0Hz), 9.26 (1H, s).

(3) 7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Compound 80)
To a suspension of tert-butyl 7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (compound 80-2) (236 mg, 0.476 mmol) in ethanol (10 mL) was added 4 M hydrochloric acid/dioxane solution (5 mL), and the mixture was heated to reflux for 1 hour. After cooling, the solvent was evaporated under reduced pressure. Ethyl acetate and diethyl ether were added to the residue, and the resulting solid was collected by filtration and dried to obtain the title compound (80) (93.0 mg).
^1H -NMR ( _CD3 OD) δ: 2.75 (3H, s), 3.25-3.33 (2H, m), 3.58-3.64 (2H, m), 4.06 (3H, s), 4.60 (2H, s), 7.13 (1H, d, J = 3.6 Hz), 7.56 (2H, d, J = 8.0Hz), 7.68-7.76 (2H, m), 8.25-8.35 (2H, m), 8.94 (1H, d, J = 8.4Hz), 10.59 (1H, s).

Example 20
Synthesis of 2-methyl-7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Compound 81)

(1) 2-methyl-7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline (Compound 81-1)
To a suspension of 7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (compound 80) (41.1 mg, 0.0954 mmol) in methanol (1 mL), sodium triacetoxyborohydride (81.0 mg, 0.382 mmol), 37% aqueous formaldehyde solution (47 μL, 0.477 μmol), and acetic acid (7 μL, 0.114 μmol) were added, and the mixture was stirred at room temperature for 13 hours. A saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered. The solvent was evaporated under reduced pressure, and the mixture was dried to give the title compound (81-1) (33.0 mg).
¹ H-NMR (CDCl ₃ ) δ: 2.53 (3H, s), 2.75 (3H, s), 2.76-2.81 (2H, m), 3.05 (2H, t, J = 6.0Hz), 3.75 (2H, s), 3.98 (3H, s), 6.83 (1H, d, J = 3.6Hz), 7.18 (1 H, d, J = 7.6Hz), 7.22 (1H, d, J = 3.6Hz), 7.31-7.38 (2H, m), 7.92 (1 H, s), 8.01 (1H, d, J = 8.0Hz), 8.64 (1H, d, J = 8.4Hz), 9.26 (1H, s).

(2) 2-methyl-7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Compound 81)
To a suspension of 2-methyl-7-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline (compound 81-1) (33.0 mg, 80.8 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.2 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and diethyl ether were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (81) (27.0 mg).
^1H -NMR ( _CD3 OD) δ: 2.75 (3H, s), 3.14 (3H, s), 3.28-3.37 (6H, m), 4.07 (3H, s), 7.13 (1H, d, J = 3.6Hz), 7.53-7.6 3 (2H, m), 7.68-7.76 (2H, m), 8.26 (1H, s), 8.32-8.38 (1H, m), 8.95 (1H, d, J = 8.8Hz), 10.56 (1H, s).

Example 21
Synthesis of 4-(isoindolin-5-yl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 93)

(1) tert-Butyl 5-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)isoindoline-2-carboxylate (Compound 93-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1-1) (150 mg, 0.742 mmol) in dioxane (7 mL), tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-isoindole-2-carboxylate (269 mg, 0.780 mmol), 1 M aqueous sodium carbonate solution (1.4 mL, 1.4 mmol), and bis(triphenylphosphine)palladium(II) dichloride (56.8 mg, 80.9 μmol) were added, and the mixture was heated to reflux for 2 hours. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The resulting solid was dissolved in dichloromethane, dried over anhydrous sodium sulfate, and then filtered. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (93-1) (193 mg, 0.501 mmol, yield 68%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.54 (9H, s), 3.90 (3H, s), 4.73-4.81 (4H, m), 6.79 (1H, dd, J = 3.7Hz, 3.7H z), 7.23 (1H, d, J = 3.7Hz), 7.42 (1H, dd, J = 7.8Hz, 19.2Hz), 8.00-8.06 (2H, m).

(2) tert-butyl 5-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)isoindoline-2-carboxylate (Compound 93-2)
To a solution of tert-butyl 5-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)isoindoline-2-carboxylate (Compound 93-1) (193 mg, 0.501 mmol) in N,N-dimethylformamide (10 mL), 4-methylbenzimidazole (128 mg, 0.968 mmol), cesium carbonate (347 mg, 1.07 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (38.4 mg, 80.6 μmol), and tris(dibenzylideneacetone)dipalladium (35.5 mg, 38.8 μmol) were added, and the mixture was heated at 160°C for 15 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The solid was dissolved in dichloromethane, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (93-2) (103 mg, 0.214 mmol, yield 43%) from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.56 (9H, s), 2.75 (3H, s), 3.99 (3H, s), 4.76-4.87 (4H, m), 6.83 ( 1H, dd, J=4.2Hz, 4.2Hz), 7.19 (1H, d, J=7.3Hz), 7.24 (1H, d, J=3.9Hz) , 7.34 (1H, ddd, J = 1.8Hz, 7.8Hz, 7.8Hz), 7.49 (1H, dd, J = 7.8Hz, 17.9 Hz), 8.09-8.18 (2H, m), 8.63 (1H, d, J=8.2Hz), 9.25 (1H, d, J=1.4Hz).

(3) 4-(isoindolin-5-yl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 93)
To a suspension of tert-butyl 5-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)isoindoline-2-carboxylate (Compound 93-2) (100 mg, 0.208 mmol) in methanol (4 mL), a 4 M hydrochloric acid/dioxane solution (0.6 mL) was added, and the mixture was heated to reflux for 1 hour. The solvent was evaporated under reduced pressure, and then diethyl ether and methanol were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (93) (87.0 mg).
^1H -NMR (DMSO- _d6 ) δ: 2.66 (3H, s), 3.99 (3H, s), 4.62-4.71 (4H, m), 7.12 (1H, d, J=3. 7Hz), 7.29 (1H, d, J = 7.3Hz), 7.46 (1H, dd, J = 7.8Hz, 7.8Hz), 7.69 ( 1H, d, J = 8.0Hz), 7.81 (1H, d, J = 3.7Hz), 8.37 (1H, d, J = 7.8Hz), 8.4 1 (1H, s), 8.65 (1H, d, J=7.8Hz), 9.73 (1H, s), 9.94-10.04 (1H, m).

Compound (95) was synthesized from compound (93) in accordance with the method for synthesizing compound (81) from compound (80).
7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(2-methylisoindolin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 95)
^1H -NMR (DMSO- _d6 ): 2.65 (3H, s), 3.17 (3H, s), 3.99 (3H, s), 4.53-4.63 (2H, m), 4.88-5 .00 (2H, m), 7.11 (1H, d, J = 3.7Hz), 7.26 (1H, d, J = 7.5Hz), 7.42 (1H, d d, J=8.2Hz, 8.2Hz), 7.70 (1H, d, J=7.5Hz), 7.81 (1H, d, J=3.7Hz), 8. 39 (1H, d, J = 8.2Hz), 8.43 (1H, s), 8.63 (1H, d, J = 8.2Hz), 9.58 (1H, s).

Compound (94) was synthesized from compound (1-1) according to the synthesis method of compound (93): 6-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (compound 94).
^1H -NMR (DMSO- _d6 ) δ: 2.65 (3H, s), 3.23 (2H, t, J = 6.2Hz), 3.43-3.50 (2H, m), 3.99 (3H, s ), 4.38-4.43 (2H, m), 7.09 (1H, d, J = 3.7Hz), 7.27 (1H, d, J = 7.3Hz), 7.4 3 (1H, dd, J = 7.8Hz, 7.8Hz), 7.51 (1H, d, J = 7.8Hz), 7.79 (1H, d, J = 3.7Hz ), 8.20-8.25 (2H, m), 8.64 (1H, d, J=8.2Hz), 9.50 (1H, s), 9.63 (1H, s).

Compound (96) was synthesized from compound (94) in accordance with the synthesis method for compound (81) from compound (80).
2-methyl-6-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Compound 96)
^1H -NMR (DMSO- _d6 ) δ: 2.66 (3H, s), 2.97-3.05 (2H, m), 3.21-3.33 (4H, m), 3.71-3.74 (1H, m), 3. 99 (3H, s), 4.38-4.43 (2H, m), 7.10 (1H, dd, J=1.4Hz, 3.7Hz), 7.29 (1H, d, J=7. 3Hz), 7.45 (1H, dd, J = 7.8Hz, 7.8Hz), 7.52 (1H, dd, J = 4.1Hz, 7.8Hz), 7.80 (1H , dd, J=1.8Hz, 3.7Hz), 8.19-8.27 (2H, m), 8.65 (1H, d, J=8.2Hz), 9.70 (1H, s).

Example 22
Synthesis of 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 39)

(1) tert-Butyl 5-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (Compound 39-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 1-1) (707 mg, 3.50 mmol) in dimethoxyethane (35 mL), tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (1.23 g, 3.57 mmol), potassium carbonate (627 mg, 4.55 mmol), water (7 mL), and tetrakis(triphenylphosphine)palladium (121 mg, 0.121 mmol) were added, and the mixture was stirred at 70°C for 2 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in methanol, filtered, and dried to obtain the title compound (39-1) (762 mg, 1.98 mmol, yield 57%).
^1H -NMR (DMSO- _d6 ) δ: 1.65 (9H, s), 3.85 (3H, s), 6.88 (1H, d, J = 3.8Hz), 7.12 (1H, d, J = 3.7Hz), 7.78 (1 H, d, J = 3.8 Hz), 7.91 (1H, d, J = 3.7 Hz), 8.81 (1H, d, J = 2.3 Hz), 9.15 (1H, d, J = 2.3 Hz).

(2) 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 39-2)
To a solution of tert-butyl 5-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (Compound 39-1) (113 mg, 0.292 mmol) in N,N-dimethylformamide (2 mL), 4-methylbenzimidazole (50.0 mg, 0.380 mmol), cesium carbonate (124 mg, 0.381 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (28.0 mg, 58.4 μmol), and tris(dibenzylideneacetone)dipalladium (27.0 mg, 29.2 μmol) were added, and the mixture was heated at 160°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The solid was suspended in methanol, filtered, and dried to obtain the title compound (39-2) (21.0 mg, 55.3 mol, yield 19%).
^1H -NMR (DMSO- _d6 ) δ: 2.63 (3H, s), 3.98 (3H, s), 6.69 (1H, dd, J=1.8Hz, 3.2Hz), 7.11 (1H, d , J=3.1Hz), 7.18 (1H, d, J=7.3Hz), 7.37 (1H, dd, J=7.3Hz, 7.8Hz), 7.63 ( 1H, d, J = 3.2Hz), 7.73 (1H, d, J = 3.7Hz), 8.62 (1H, d, J = 7.8Hz), 8.93 (1H, d, J=2.0Hz), 9.21 (1H, d, J=2.0Hz), 9.36 (1H, s), 12.02 (1H, d, J=1.8Hz).

(3) 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 39)
To a suspension of 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 39-2) (21.0 mg, 55.3 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to give the title compound (39) (15.2 mg).
^1H -NMR (DMSO- _d6 ) δ: 2.64 (3H, s), 3.99 (3H, s), 6.69 (1H, dd, J=1.8Hz, 3.2Hz), 7.11 (1H, d , J=3.1Hz), 7.20 (1H, d, J=7.3Hz), 7.38 (1H, dd, J=7.3Hz, 7.8Hz), 7.63 ( 1H, d, J = 3.2Hz), 7.73 (1H, d, J = 3.7Hz), 8.62 (1H, d, J = 7.8Hz), 8.94 (1H, d, J=2.0Hz), 9.22 (1H, d, J=2.0Hz), 9.51 (1H, s), 12.02 (1H, d, J=1.8Hz).

Example 23
Synthesis of 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 32)

(1) 4-(benzyloxy)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 32-1)
To a solution of 4-(benzyloxy)-2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 7-1) (5.01 g, 18.3 mmol) in N,N-dimethylformamide (50 mL), 4-methylbenzimidazole (2.92 g, 21.9 mmol), cesium carbonate (7.87 g, 24.1 mmol), tris(dibenzylideneacetone)dipalladium (0.844 g, 0.913 mmol), and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.882 g, 1.85 mmol) were added, and the mixture was heated to 130°C under an argon atmosphere and stirred for 3 hours. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The resulting solid was dissolved in dichloromethane, dried over anhydrous sodium sulfate, and then filtered. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (32-1) (2.07 g, 5.60 mmol, yield 31%) was obtained from the dichloromethane:ethyl acetate (5:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 2.73 (3H, s), 3.91 (3H, s), 5.70 (2H, s), 6.59 (1H, d, J = 3.2Hz), 7.00 (1H, d, J = 3.2Hz), 7.13-7.19 ( 1H, m), 7.27-7.37 (2H, m), 7.38-7.44 (2H, m), 7.53-7.57 (2H, m), 8.49 (1H, d, J = 7.8Hz), 9.06 (1H, s).

(2) 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (Compound 32-2)
Palladium-activated carbon (Pd 10%) (1.08 g, 0.101 mmol) was added to a solution of 4-(benzyloxy)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 32-1) (3.72 g, 10.1 mmol) in acetic acid (100 mL) and dichloromethane (50 mL), and the mixture was stirred under a hydrogen gas atmosphere for 14 hours. The reaction mixture was filtered through Celite, and the solvent was evaporated under reduced pressure. Dichloromethane and saturated aqueous sodium bicarbonate solution were added to the residue, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was washed with a dichloromethane:diethyl ether mixture and dried to obtain the title compound (32-2) (1.52 g, 5.44 mmol, yield 54%).
¹ H-NMR (DMSO-d ₆ ) δ: 2.60 (3H, s), 3.82 (3H, s), 6.52-6.56 (1H, m), 7.14-7.34 (3H, m), 8.27-8.47 (1H, m), 8.95 (1H, s), 12.44 (1H, brs).

(3) 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (Compound 32-3)
Triethylamine (1.63 mL, 11.7 mmol) was added to a solution of 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (compound 32-2) (1.63 g, 5.84 mmol) and p-toluenesulfonyl chloride (1.22 g, 6.24 mmol) in N,N-dimethylformamide (30 mL), and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into ice water, and the precipitate was collected by filtration. After washing with methanol and drying, the title compound (32-3) (2.33 g, 5.37 mmol, yield 91%) was obtained.
^1H -NMR (DMSO- _d6 ) δ: 2.40 (3H, s), 2.56 (3H, s), 3.88 (3H, s), 6.65 (1H, d, J = 3.7Hz), 7.18 (1H, d, J = 7.3Hz), 7.25 (1H, t, J = 7.3H z), 7.54 (2H, d, J = 7.8Hz), 7.69 (1H, d, J = 3.7Hz), 8.02 (2H, d, J = 8.2Hz), 8.17 (1H, d, J = 8.2Hz), 8.71 (1H, s).

(4) tert-Butyl 5-(7-methyl-2-(4-methyl-1H-benzo[d]idazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (Compound 32-4)
7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (compound 32-3) (141 mg, 0.326 mmol) in dimethoxyethane (3.2 mL) solution, tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H,2H,3H-pyrrolo[2,3-b]pyridine-1-carboxylate (135 mg, 0.391 mmol), potassium carbonate (67.0 mg, 0.488 mmol), water (0.6 mL), tetrakis(triphenylphosphine)palladium (37.0 mg, 32.0 μmol) was added, and the mixture was heated at 110 ° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (32-4) (135 mg, 0.280 mmol, yield 86%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.61 (9H, s), 2.75 (3H, s), 3.24 (2H, t, J = 8.2Hz), 3.98 (3H, s), 4 .14 (2H, t, J = 8.2Hz), 6.48 (1H, d, J = 3.7Hz), 7.19 (1H, d, J = 7.3Hz), 7.24 (1H, d, J = 3.7Hz), 7.35 (1H, dd, J = 7.3Hz, 8.2Hz), 8.33 (1H, d, J = 2.3Hz), 8.61 (1H, d, J = 8.2Hz), 9.14 (1H, d, J = 2.3Hz), 9.2 (1H, s).

(5) 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 32)
To a suspension of tert-butyl 5-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (compound 32-4) (135 mg, 0.280 mmol) in ethanol (8 mL), a 4 M hydrochloric acid/dioxane solution (4 mL) was added, and the mixture was stirred at 70°C for 1 hour. After cooling, the solvent was evaporated under reduced pressure. Ethyl acetate was added to the residue, and the resulting solid was collected by filtration and dried to obtain the title compound (32) (128 mg).
^1H -NMR (DMSO- _d6 ) δ: 2.61 (3H, s), 3,27 (2H, t, J = 8.2Hz), 3.88 (2H, t, J = 8.2Hz), 3.93 (3H, s), 7.05 (1H, d, J = 3.7Hz), 7.20 (1H, d, J = 7.3Hz), 7.36 (1H, dd, J=7.3Hz, 8.2Hz), 7.74 (1H, d, J=3.7Hz), 8.52 (1H, d, J=1.4Hz), 8.5 4 (1H, d, J = 8.2Hz), 8.57 (1H, d, J = 1.4Hz), 9.03 (1H, s), 9.52 (1H, s).

Example 24
Synthesis of 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methylindolin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 33)

(1) 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methylindolin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 33-1)
To a solution of 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (Compound 32-3) (79.0 mg, 0.182 mmol) in dimethoxyethane (2 mL), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (56.0 mg, 0.218 mmol), potassium carbonate (37.0 mg, 0.273 mmol), water (0.4 mL), and tetrakis(triphenylphosphine)palladium (21.0 mg, 18.1 μmol) were added, and the mixture was heated at 110° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (33-1) (34.0 mg, 86.2 μmol, yield 47%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 2.63 (3H, s), 2.85 (3H, s), 3,03 (2H, t, J = 8.2Hz), 3.45 (2H, t, J = 8.2 Hz), 3.95 (3H, s), 6.66 (1H, d, J = 8.2Hz), 7.01 (1H, d, J = 3.7Hz), 7.25 (1 H, d, J = 7.3Hz), 7.42 (1H, dd, J = 7.3Hz, 8.2Hz), 7.64 (1H, d, J = 3.7Hz), 8 .13 (1H, s), 8.13 (1H, d, J = 8.2Hz), 8.64 (1H, d, J = 8.2Hz), 9.45 (1H, s).

(2) 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methylindolin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 33)
To a suspension of 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methylindolin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 33-1) (34.0 mg, 86.2 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (33) (31.3 mg).
^1H -NMR (DMSO- _d6 ) δ: 2.64 (3H, s), 2.85 (3H, s), 3,08 (2H, t, J = 8.2Hz), 3.47 (2H, t, J = 8.2 Hz), 3.94 (3H, s), 6.69 (1H, d, J = 8.2Hz), 7.02 (1H, d, J = 3.7Hz), 7.26 (1 H, d, J = 7.3Hz), 7.42 (1H, dd, J = 7.3Hz, 8.2Hz), 7.65 (1H, d, J = 3.7Hz), 8 .14 (1H, s), 8.15 (1H, d, J=8.2Hz), 8.64 (1H, d, J=8.2Hz), 9.59 (1H, s).

Compound (83) was synthesized from compound (32-3) according to the synthesis method of compound (33).
7-Methyl-3-(7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5,6,7,8-tetrahydro-1,7-naphthyridine hydrochloride (Compound 83)
^1H -NMR ( _CD3 OD) δ: 2.76 (3H, s), 3.19 (3H, s), 3.28-3.33 (6H, m), 4.10 (3H, s), 7.18 (1H, d, J = 3.6Hz), 7.58 (1H, d, J = 7.2Hz), 7.73 (1H , dd, J = 7.6Hz, 8.0Hz), 7.80 (1H, d, J = 3.6Hz), 8.75 (1H, s), 8.95 (1H, d, J = 8.8Hz), 9.47 (1H, d, J = 1.6Hz), 10.63 (1H, s).

Example 25
Synthesis of 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 34)

(1) 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 34-1)
To a solution of 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 32) (99.0 mg, 0.237 mmol) in N,N-dimethylformamide (3 mL), sodium hydride (60% oil dispersion) (24.0 mg, 0.593 mmol) and iodomethane (17.7 μL, 0.284 mmol) were added under ice cooling, and the mixture was then warmed to room temperature and stirred for 1 hour. Water was added to the reaction solution, which was then extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (34-1) (17.0 mg, 43.0 μmol, yield 18%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 2.75 (3H, s), 3.08 (3H, s), 3.16 (2H, t, J = 8.2Hz), 3.66 (2H, t, J = 8.2Hz), 3.95 (3H, s), 6.82 (1H, d, J = 3.7Hz), 7.17 (1H, d, J = 3.7Hz), 7.18 (1H, d, J = 7.8Hz), 7.34 (1H, dd, J = 7.8Hz, 7.8Hz), 8.10 (1H, d, J = 1.8Hz), 8.62 (1H, d, J = 7.8Hz), 8.85 (1H, d, J = 1.8Hz), 9.23 (1H, s).

(2) 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 34)
To a suspension of 7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 34-1) (17.0 mg, 43.0 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and stirred for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to give the title compound (34) (14.2 mg).
^1H -NMR (DMSO- _d6 ) δ: 2.61 (3H, s), 2.99 (3H, s), 3.11 (2H, t, J=8.2Hz), 3.66 (2H, t, J= 8.2Hz), 3.93 (3H, s), 7.03 (1H, d, J = 3.7Hz), 7.20 (1H, d, J = 7.3Hz), 7.36 (1H, dd, J = 7.3Hz, 8.2Hz), 7.65 (1H, d, J = 3.7Hz), 8.52 (1H, d, J = 1.4Hz), 8.54 (1H, d, J = 8.2Hz), 8.57 (1H, d, J = 1.4Hz), 9.49 (1H, s).

Example 26
Synthesis of 5-(5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-3-amine hydrochloride (Compound 35)

(1) 2,4-Dichloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine (Compound 35-1)
To a solution of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (1.60 g, 8.51 mmol) in acetonitrile (42 mL), 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (4.80 g, 13.5 mmol) and acetic acid (8.50 mL, 0.148 mol) were added, and the mixture was stirred at 80°C for 3 hours. After cooling, the reaction solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (35-1) (644 mg, 3.13 mmol, yield 37%) was obtained from the n-hexane:ethyl acetate (4:1) fraction.
¹ H-NMR (DMSO-d ₆ ) δ: 7.77 (1H, d, J=2.4Hz), 7.97 (1H, d, J=2.4Hz).

(2) 2,4-Dichloro-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 35-2)
To a solution of 2,4-dichloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine (compound 35-1) (3.22 g, 15.6 mmol) in N,N-dimethylformamide (70 mL), potassium carbonate (3.22 g, 23.3 mmol) and iodomethane (1.16 mL, 18.7 mmol) were added under ice cooling, and the mixture was stirred for 2 hours. Water (200 mL) was added to the reaction solution, and the precipitated solid was collected by filtration and dried to obtain the title compound (35-2) (3.05 g, 13.9 mmol, yield 89%).
¹ H-NMR (DMSO-d ₆ ) δ: 3.76 (3H, s), 7.82 (1H, d, J=2.2Hz).

(3) 4-(benzyloxy)-2-chloro-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 35-3)
To a solution of 2,4-dichloro-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 35-2) (3.05 g, 13.9 mmol) in N,N-dimethylformamide (130 mL), benzyl alcohol (1.72 mL, 16.6 mmol) and sodium hydride (60% oil dispersion) (831 mg, 20.7 mmol) were added under ice cooling, and the mixture was stirred for 40 minutes. Water was added to the reaction solution, and the precipitated solid was collected by filtration and purified by silica gel column chromatography. The title compound (35-3) (3.67 g, 12.5 mmol, yield 91%) was obtained from the n-hexane:ethyl acetate (3:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.75 (3H, s), 5.61 (2H, s), 6.72 (1H, d, J=2.8Hz), 7.32-7.53 (5H, m).

(4) 4-(benzyloxy)-5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 35-4)
To a solution of 4-(benzyloxy)-2-chloro-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 35-3) (3.67 g, 12.5 mmol) in N,N-dimethylformamide (125 mL), 4-methylbenzimidazole (1.80 g, 13.8 mmol), cesium carbonate (5.32 g, 16.3 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (598 mg, 1.25 mmol), and tris(dibenzylideneacetone)dipalladium (575 mg, 0.629 mmol) were added, and the mixture was stirred at 130°C for 1 hour. After cooling, water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in methanol, filtered, and dried to obtain the title compound (35-4) (3.90 g, 10.1 mmol, yield 81%).
^1H -NMR (DMSO- _d6 ) δ: 2.61 (3H, s), 3.84 (3H, s), 5.79 (2H, s), 7.18 (1H, d, J = 7.3Hz), 7.31- 7.45 (5H, m), 7.58 (2H, d, J = 6.9Hz), 8.45 (1H, d, J = 8.7Hz), 9.20 (1H, s).

(5) 5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (Compound 35-5)
Palladium-activated carbon (Pd 10%) (500 mg, 0.470 mmol) was added to a solution of 4-(benzyloxy)-5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 35-4) (3.90 g, 10.1 mmol) in chloroform (70 mL) and methanol (70 mL), and the mixture was stirred at room temperature under a hydrogen gas atmosphere for 18 hours. The reaction mixture was filtered through Celite, and the solvent was evaporated under reduced pressure. The residue was suspended in methanol, filtered, and dried to obtain the title compound (35-5) (2.62 g, 8.81 mmol, 87% yield).
¹ H-NMR (DMSO-d ₆ ) δ: 2.60 (3H, s), 3.76 (3H, s), 7.18-7.37 (3H, m), 8.20-8.42 (1H, m), 8.62 (1H, brs), 9.05 (1H, s).

(6) 5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (Compound 35-6)
To a solution of 5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol (compound 35-5) (2.62 g, 8.81 mmol) in N,N-dimethylformamide (70 mL), triethylamine (2.45 mL, 17.6 mmol) and p-toluenesulfonyl chloride (1.84 g, 9.70 mmol) were added and stirred at room temperature for 20 minutes. Water was added to the reaction solution, and the precipitated solid was collected by filtration. The solid was suspended in methanol, collected by filtration, and dried to obtain the title compound (35-6) (3.95 g, 8.75 mmol, yield 99%).
^1H -NMR (DMSO- _d6 ) δ: 2.44 (3H, s), 2.58 (3H, s), 3.86 (3H, s), 7.18 (1H, d, J = 7.1Hz), 7.24 (1H, dd, J = 7.1Hz, 7.8Hz), 7.5 5 (2H, d, J = 8.7Hz), 7.71 (1H, d, J = 2.3Hz), 8.02 (2H, d, J = 8.7Hz), 8.10 (1H, d, J = 7.8Hz), 8.69 (1H, s).

(7) 5-(5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-3-amine (Compound 35-7)
5-Fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (compound 35-6) (98.0 mg, 0.217 mmol) in dimethoxyethane (2.1 mL) solution, N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (43.2 mg, 0.260 mmol), potassium carbonate (44.9 mg, 0.325 mmol), water (0.6 mL), tetrakis(triphenylphosphine)palladium (25.1 mg, 21.7 μmol) was added and heated at 110 ° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (35-7) (28.0 mg, 69.7 mmol, yield 32%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 2.62 (3H, s), 3.18 (6H, s), 3.95 (3H, s), 7.23 (1H, d, J = 7.7Hz), 7.37 (1H, dd, J = 7.7Hz, 7.7Hz), 7.89 (1H, d, J = 2.3Hz), 8.24 (1H, s), 8.37 (1H, s), 8.54 (1H, d, J = 7.7Hz), 8.76 (1H, s), 9.40 (1H, s).

(8) 5-(5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-3-amine hydrochloride (Compound 35)
To a suspension of 5-(5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-3-amine (compound 35-7) (28.0 mg, 69.7 mmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (35) (20.4 mg).
^1H -NMR (DMSO- _d6 ) δ: 2.63 (3H, s), 3.18 (6H, s), 3.95 (3H, s), 7.24 (1H, d, J = 7.7Hz), 7.39 (1H, dd, J = 7.7Hz, 7.7Hz), 7.90 (1H, d, J = 2.3Hz), 8.24 (1H, s), 8.39 (1H, s), 8.54 (1H, d, J = 7.7Hz), 8.76 (1H, s), 9.50 (1H, s).

Compound (37) was synthesized from compound (35-6) according to the synthesis method of compound (35).
5-Fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 37)
^1H -NMR (DMSO- _d6 ) δ: 2.65 (3H, s), 3.93 (3H, s), 3.94 (3H, s), 6.70 (1H, d, J = 3.7Hz), 7.30 (1H, d, J = 7.8Hz), 7.47 (1H, dd, J = 7.8Hz, 7.8Hz), 7.70 (1H, d, J = 3.7Hz), 7.81 (1H, d, J = 2.3Hz), 8.63 (1H, d, J = 7.8Hz), 8.75 (1H, dd, J=2.3Hz, 2.3Hz), 9.07 (1H, dd, J=2.3Hz, 2.3Hz), 9.77 (1H, s).

Compound (36) was synthesized from compound (35-6) according to the method for synthesizing compound (32) from compound (32-3).
4-(2,3-Dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 36)
^1H -NMR (DMSO- _d6 ) δ: 2.63 (3H, s), 3.28 (2H, t, J = 8.2Hz), 3.90 (3H, s), 3.92 (2H, t, J = 8.2Hz), 7.23 (1H, d, J = 7.8Hz), 7.38 (1H, dd, J = 7.8Hz, 7.8Hz), 7.79 (1H, d, J = 1.8Hz), 8.36 (1H, s), 8.38 (1H, s), 8.51 (1H, d, J = 7.8Hz), 9.29 (1H, s), 9.49 (1H, s).

Compound (38) was synthesized from compound (36) in accordance with the synthesis method for compound (34) from compound (32).
5-Fluoro-7-methyl-2-(4-methyl-1H-benzo[d]imidazol-1-yl)-4-(1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 38)
^1H -NMR (DMSO- _d6 ) δ: 2.62 (3H, s), 2.99 (3H, s), 3.10 (2H, t, J = 8.7Hz), 3.62 (2H, t, J = 8.7Hz), 3.87 (3H, s), 7.21 (1H, d, J = 7.1Hz), 7. 36 (1H, dd, J = 7.1Hz, 8.2Hz), 7.65 (1H, d, J = 2.3Hz), 8.03 (1H, s), 8.53 (1H, d, J = 8.2Hz), 8.62 (1H, s), 9.43 (1H, s).

Example 27
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(3-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 51)

(1) 2-chloro-5-fluoro-4-(3-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 51-1)
To a solution of 2,4-dichloro-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 35-2) (103 mg, 0.467 mmol) in dioxane (4.7 mL), 3-methoxyphenylboronic acid (78.0 mg, 0.513 mmol), potassium carbonate (96.7 mg, 0.701 mmol), water (0.8 mL), and bis(triphenylphosphine)palladium(II) dichloride (6.60 mg, 9.34 μmol) were added and heated at 110°C for 2 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (51-1) (114 mg, 0.391 mmol, 84% yield) was obtained from the n-hexane:ethyl acetate (4:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.86 (3H, s), 3.91 (3H, s), 7.01 (1H, d, J = 2.8Hz), 7.07-7.12 (1H , m), 7.45 (1H, dd, J=7.8Hz, 8.2Hz), 7.59 (1H, s), 7.62-7.67 (1H, m).

(2) 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(3-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 51-2)
A solution of 2-chloro-5-fluoro-4-(3-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 51-1) (113 mg, 0.387 mmol) in toluene (4 mL) was placed in a sealed reaction vessel, and benzimidazole (55.0 mg, 0.465 mmol), tripotassium phosphate (164 mg, 0.774 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (18.6 mg, 39.0 μmol), and tris(dibenzylideneacetone)dipalladium (10.6 mg, 11.6 μmol) were added, followed by heating at 120°C for 7 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by preparative TLC (preparative thin layer chromatography), and the title compound (51-2) (60.8 mg, 0.163 mmol, yield 42%) was obtained from the dichloromethane:methanol (30:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.95 (6H, s), 7.02 (1H, d, J = 2.3Hz), 7.12-7.17 (1H, m), 7.36-7.48 (2H, m), 7.52 (1H, dd, J = 7.8Hz , 8.2Hz), 7.73 (1H, s), 7.75-7.81 (1H, m), 7.88 (1H, d, J = 8.2Hz), 8.78 (1H, d, J = 7.8Hz), 9.27 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(3-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 51)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(3-methoxyphenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 51-2) (54.5 mg, 0.146 mmol) in methanol (6 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 1 hour. After the solvent was evaporated under reduced pressure, ethyl acetate was added to the residue, and the resulting solid was collected by filtration and dried to obtain the title compound (51) (46.7 mg).
^1H -NMR ( _CD3 OD) δ: 3.92 (3H, s), 4.00 (3H, s), 7.19 (1H, dd, J = 2.5Hz, 8.2Hz), 7.52 (1H, dd, J = 7.6Hz, 8.2Hz), 7.58 (1H, d, J = 2.8Hz), 7.70-7.82 (3H, m), 7.73 (1H, s), 7.93 (1H, d, J = 8.2Hz), 9.06 (1H, d, J = 8.2Hz), 10.37 (1H, s).

Compounds (52) and (53) were synthesized from compound (35-2) according to the synthesis method of compound (51).
2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 52)
^1H -NMR ( _CD3 OD) δ: 4.01 (3H, s), 7.33-7.42 (2H, m), 7.60 (1H, d, J = 2.3Hz), 7.70-7.84 (2H, m) , 7.95 (1H, d, J = 8.4Hz), 8.24-8.31 (2H, m), 9.06 (1H, d, J = 8.4Hz), 10.42 (1H, s).

5-(2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline hydrochloride (Compound 53)
^1H -NMR ( _CD3 OD) δ: 3.13 (6H, s), 4.04 (3H, s), 7.40-7.48 (1H, m), 7.63 (1H, d, J=2.3Hz), 7.72-7.85 (2H, m), 7. 97 (1H, d, J = 7.8Hz), 7.97-8.04 (1H, m), 8.05-8.12 (1H, m), 9.09 (1H, d, J = 8.7Hz), 10.41 (1H, s).

Example 28
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(5-(methoxymethyl)pyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 60)

(1) 2-chloro-5-fluoro-4-(5-(methoxymethyl)pyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 60-1)
To a solution of 2,4-dichloro-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 35-2) (90.3 mg, 0.410 mmol) in dioxane (4 mL), (5-(methoxymethyl)pyridin-3-yl)boronic acid (90.3 mg, 0.410 mmol), potassium carbonate (85.0 mg, 0.615 mmol), water (0.8 mL), and bis(triphenylphosphine)palladium(II) dichloride (5.80 mg, 8.20 μmol) were added, and the mixture was heated at 140 ° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (60-1) (73.9 mg, 0.241 mmol, yield 59%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.46 (3H, s), 3.87 (3H, s), 4.60 (2H, s), 7.05 (1H, d, J = 2.8Hz), 8.3 2-8.36 (1H, m), 8.74 (1H, d, J = 1.8Hz), 9.16 (1H, dd, J = 2.6Hz, 5.2Hz).

(2) 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(5-(methoxymethyl)pyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 60-2)
To a solution of 2-chloro-5-fluoro-4-(5-(methoxymethyl)pyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 60-1) (72.9 mg, 0.238 mmol) in N,N-dimethylformamide (2 mL), benzimidazole (33.7 mg, 0.285 mmol), cesium carbonate (116 mg, 0.357 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (22.7 mg, 47.6 μmol), and tris(dibenzylideneacetone)dipalladium (10.9 mg, 11.9 μmol) were added, and the mixture was heated at 160 ° C. for 5 minutes using a microwave synthesizer. After cooling, the reaction mixture was filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (60-2) (75.2 mg, 0.194 mmol, yield 81%) was obtained from the chloroform fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.49 (3H, s), 3.95 (3H, s), 4.64 (2H, s), 7.04 (1H, d, J = 2.8Hz), 7.35-7.47 (2H, m), 7.87 (1H, d, J = 7.3Hz), 8.40-8.43 (1H, m), 8.72 (1H, d, J = 7.3Hz), 8.76 (1H, d, J = 2.3Hz), 9.24 (1H, s), 9.30 (1H, dd, J = 2.4Hz, 4.8Hz).

(3) 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(5-(methoxymethyl)pyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 60)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-4-(5-(methoxymethyl)pyridin-3-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 60-2) (75.2 mg, 0.194 mmol) in methanol (5 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (60) (83.4 mg).
^1H -NMR ( _CD3 OD) δ: 3.59 (3H, s), 4.09 (3H, s), 4.86 (2H, s), 7.72-7.88 (3H, m), 7.98 (1H , d, J=8.0Hz), 9.00-9.10 (2H, m), 9.30 (1H, s), 9.61 (1H, s), 10.60 (1H, s).

Compounds (59) and (61) were synthesized from compound (35-2) according to the synthesis method of compound (60).
2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-4-(2-methylpyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 59)
^1H -NMR ( _CD3 OD) δ: 2.99 (3H, s), 4.10 (3H, s), 7.71-7.87 (3H, m), 7.97 (1H, d, J = 7.8Hz), 8.66 (1H, d, J = 6.2Hz), 8.75 (1H, s), 8.99 (1H, d, J = 6.2Hz), 9.03 (1H, d, J = 8.8Hz), 10.40-10.60 (1H, m).

5-(2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine hydrochloride (Compound 61)
^1H -NMR ( _CD3 OD) δ: 3.44 (6H, s), 4.05 (3H, s), 7.52 (1H, d, J = 9.8Hz), 7.70 (1H, d, J = 2.3Hz), 7.72-7.84 (2H, m), 7.96 (1H , d, J=7.8Hz), 8.80 (1H, d, J=1.8Hz), 8.91 (1H, dd, J=1.8Hz, 9.8Hz), 9.03 (1H, d, J=8.4Hz), 10.46 (1H, s).

Example 29
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 97)

(1) 2-(1H-benzo[d]imidazol-1-yl)-4-(benzyloxy)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 97-1)
To a solution of 4-(benzyloxy)-2-chloro-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 35-3) (2.90 g, 9.94 mmol) in N,N-dimethylformamide (100 mL), benzimidazole (1.29 g, 10.9 mmol), cesium carbonate (4.87 g, 14.9 mmol), tris(dibenzylideneacetone)dipalladium (0.477 g, 0.521 mmol), and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (501 mg, 1.05 mmol) were added, and the mixture was stirred for 3 hours at 130°C. After cooling, water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was washed with saturated brine, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the n-hexane:ethyl acetate (2:1) fraction was concentrated to obtain the title compound (97-1) (1.44 g, 3.86 mmol, yield 39%).
¹ H-NMR (CDCl ₃ ) δ: 3.85 (3H, s), 5.74 (2H, s), 6.75 (1H, d, J = 2.8Hz), 7.32-7.44 (5H, m) , 7.54-7.58 (2H, m), 7.84-7.87 (1H, m), 8.58-8.62 (1H, m), 9.06 (1H, s).

(2) 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol (Compound 97-2)
Palladium-activated carbon (Pd 10%) (0.533 g, 0.501 mmol) was added to a solution of 2-(1H-benzo[d]imidazol-1-yl)-4-(benzyloxy)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 97-1) (1.87 g, 5.01 mmol) in dichloromethane (30 mL) and methanol (30 mL), and the mixture was stirred at room temperature under a hydrogen gas atmosphere for 14 hours. After filtering the reaction solution, the solvent was evaporated under reduced pressure. The residue was suspended in ethanol, filtered, and dried to obtain the title compound (97-2) (996 mg, 3.51 mmol, 70% yield).
^1H -NMR (DMSO- _d6 ) δ: 3.76 (3H, s), 7.19 (1H, s), 7.38 (1H, ddd, J = 1.4Hz, 7.6Hz, 7.6Hz), 7.45 (1H, d dd, J=1.4Hz, 7.6Hz, 7.6Hz), 7.78 (1H, d, J=8.2Hz), 8.50 (1H, brs), 8.97 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl 4-methylbenzenesulfonate (Compound 97-3)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol (compound 97-2) (1.00 g, 3.53 mmol) in N,N-dimethylformamide (40 mL), triethylamine (1.00 mL, 7.17 mmol) and p-toluenesulfonyl chloride (742 mg, 3.89 mmol) were added and stirred at room temperature for 1 hour. The reaction solution was poured into ice water, and the precipitated solid was collected by filtration. The obtained solid was washed with methanol and then dried to obtain the title compound (97-3) (1.51 g, 3.45 mmol, yield 98%).
¹ H-NMR (CDCl ₃ ) δ: 2.48 (3H, s), 3.89 (3H, s), 6.91 (1H, d, J = 2.8Hz), 7.36-7.44 (4H, m), 7 .81-7.85 (1H, m), 8.03 (2H, d, J=8.2Hz), 8.47-8.50 (1H, m), 8.74 (1H, s).

(4) tert-Butyl 5-(2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (Compound 97-4)
2- (1H-benzo [d] imidazol-1-yl) -5-fluoro-7-methyl-7H-pyrrolo [2,3-d] pyrimidin-4-yl 4-methylbenzenesulfonate (compound 97-3) (100 mg, 0.229 mmol) in dimethoxyethane (2 mL) solution, tert- butyl 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -2,3-dihydropyrrolo [2,3-b] pyridine-1-carboxylate (98.5 mg, 0.286 mmol), potassium carbonate (43.9 mg, 0.318 mmol), tetrakis (triphenylphosphine) palladium (32.3 mg, 28.0 μmol), water (0.4 mL) was added, and heated at 120 ° C. for 15 minutes using a microwave synthesis apparatus. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The resulting solid was dissolved in dichloromethane, dried over anhydrous sodium sulfate, and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (97-4) (62.3 mg, 0.156 mmol, yield 68%) was obtained from the dichloromethane:ethyl acetate (1:2) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.61 (9H, s), 3.21 (2H, t, J = 8.6Hz), 3.89 (3H, s), 4.13 (2H, t, J = 8.6Hz ), 6.96 (1H, d, J = 2.8Hz), 7.38 (1H, ddd, J = 1.4Hz, 7.6Hz, 7.6Hz), 7.44 (1H, ddd, J=1.4Hz, 7.6Hz, 7.6Hz), 7.87 (1H, d, J=7.3Hz), 8.18 (1H, dd, J=1.8H z, 1.8Hz), 8.69-8.73 (1H, m), 9.06 (1H, dd, J=2.2Hz, 2.2Hz), 9.20 (1H, s).

(5) 2-(1H-benzo[d]imidazol-1-yl)-4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 97)
To a suspension of tert-butyl 5-(2-(1H-benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (compound 97-4) (62.2 mg, 0.156 mmol) in methanol (6 mL), 4 M hydrochloric acid/dioxane solution (0.6 mL) was added and the mixture was heated to reflux for 90 minutes. After cooling, the solvent was evaporated under reduced pressure, and diethyl ether and methanol were added to the residue. The resulting solid was collected by filtration and dried to give the title compound (97) (43.3 mg).
^1H -NMR ( _CD3 OD) δ: 3.42 (2H, t, J = 8.2Hz), 4.04 (3H, s), 4.07 (2H, t, J = 8.2Hz), 7.68 (1H, d, J = 2.3Hz), 7.73-7.79 (1H, m), 7.83 (1H, ddd, J=1.1Hz, 7.9Hz7.9Hz), 7.97 (1H, d, J=8.2Hz), 8.44-8.46 (1H, m), 8.49-8.52 (1H, m), 9.05 (1H, d, J=8.7Hz), 10.54 (1H, s).

Compound (98) was synthesized from compound (97) in accordance with the synthesis method for compound (34) from compound (32).
2-(1H-Benzo[d]imidazol-1-yl)-5-fluoro-7-methyl-4-(1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 98)
^1H -NMR ( _CD3 OD) δ: 3.25 (3H, s), 3.37 (2H, t, J = 8.2Hz), 4.00 (3H, s), 4.06 (2H, t, J = 8.2Hz), 7.62 (1H, d, J = 2.3Hz), 7.65- 7.71 (1H, m), 7.72-7.77 (1H, m), 7.90-7.94 (1H, m), 8.36-8.40 (2H, m), 8.94 (1H, d, J = 8.2Hz), 10.22 (1H, s).

Example 30
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-7-ethyl-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 43)

(1) 2,4-Dichloro-7-ethyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 43-1)
To a solution of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (495 mg, 2.63 mmol) in N,N-dimethylformamide (13 mL), potassium carbonate (545 mg, 3.95 mmol) and ethyl iodide (0.252 mL, 3.15 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (43-1) (548 mg, 2.54 mmol, yield 96%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.50 (3H, t, J = 7.3Hz), 4.31 (2H, q, J = 7.3Hz), 6.62 (1H, d, J = 3.2Hz), 7.26 (1H, d, J = 3.2Hz).

(2) 2-chloro-7-ethyl-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 43-2)
To a solution of 2,4-dichloro-7-ethyl-7H-pyrrolo[2,3-d]pyrimidine (compound 43-1) (84.8 mg, 0.392 mmol) in dioxane (4 mL), 4-fluorophenylboronic acid (52.6 mg, 0.431 mmol), potassium carbonate (81.2 mg, 0.588 mmol), water (0.6 mL), and bis(triphenylphosphine)palladium(II) dichloride (5.50 mg, 7.80 μmol) were added, and the mixture was heated at 110°C for 2 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (43-2) (93.0 mg, 0.337 mmol, yield 86%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ δ: 1.52 (3H, t, J = 7.4Hz), 4.35 (2H, q, J = 7.4Hz), 6.79 (1H, d, J = 3.7 Hz), 7.20-7.27 (2H, m), 7.29 (1H, d, J=3.7Hz), 8.11-8.17 (2H, m).

(3) 2-(1H-benzo[d]imidazol-1-yl)-7-ethyl-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 43-3)
A solution of 2-chloro-7-ethyl-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 43-2) (87.3 mg, 0.316 mmol) in dioxane (3 mL) was placed in a sealed reaction vessel, and benzimidazole (45.0 mg, 0.380 mmol), cesium carbonate (155 mg, 0.474 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (15.1 mg, 30.0 μmol), and tris(dibenzylideneacetone)dipalladium (5.80 mg, 6.30 μmol) were added, followed by heating at 100°C for 9 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (43-3) (46.3 mg, 0.130 mmol, yield 41%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.62 (3H, t, J = 7.3Hz), 4.45 (2H, q, J = 7.3Hz), 6.84 (1H, d, J = 3.7Hz), 7.28-7.35 (3H, m), 7.37-7.43 ( 1H, m), 7.44-7.50 (1H, m), 7.90 (1H, d, J = 7.3Hz), 8.24-8.30 (2H, m), 8.78 (1H, d, J = 7.3Hz), 9.29 (1H, s).

(4) 2-(1H-benzo[d]imidazol-1-yl)-7-ethyl-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 43)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-7-ethyl-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 43-3) (45.0 mg, 0.126 mmol) in methanol (5 mL), 4 M hydrochloric acid/dioxane solution (0.4 mL) was added and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (43) (35.4 mg).
^1H -NMR ( _CD3 OD) δ: 1.60 (3H, t, J = 7.4Hz), 4.54 (2H, q, J = 7.4Hz), 7.09 (1H, d, J = 3.9Hz), 7.36-7.44 (2H, m), 7.71-7.76 (1H, m), 7.7 7 (1H, d, J = 3.9Hz), 7.79-7.85 (1H, m), 7.95 (1H, d, J = 8.2Hz), 8.39-8.45 (2H, m), 9.09 (1H, d, J = 8.2Hz), 10.45 (1H, s).

Example 31
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-7-(difluoromethyl)-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 20)

(1) 2,4-Dichloro-7-(difluoromethyl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 20-1)
To a solution of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (1.00 g, 5.31 mmol) in methanol:water (1:1) (66 mL) was added potassium hydroxide (5.90 g, 10.5 mmol) and diethyl (bromodifluoromethyl)phosphonate (1.89 mL, 10.6 mmol) under ice cooling, and the mixture was then warmed to room temperature and stirred for 2 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (20-1) (580 mg, 2.43 mmol, yield 46%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (DMSO-d ₆ ) δ: 6.94 (1H, d, J = 3.7Hz), 8.07 (1H, d, J = 3.7Hz), 8.12 (1H, t, J = 58.4Hz).

(2) 2-chloro-7-(difluoromethyl)-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 20-2)
To a solution of 2,4-dichloro-7-(difluoromethyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 20-1) (80.0 mg, 0.336 mmol) in dioxane (3 mL), 3-pyridylboronic acid (43.0 mg, 0.352 mmol), 1 M aqueous sodium carbonate solution (0.60 mL, 0.60 mmol), and bis(triphenylphosphine)palladium(II) dichloride (23.6 mg, 33.6 μmol) were added, and the mixture was heated at 130°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (20-2) (70.0 mg, 0.249 mmol, yield 74%) was obtained from the n-hexane:ethyl acetate (1:5) fraction.
^1H -NMR (DMSO- _d6 ) δ: 7.31 (1H, d, J = 3.7Hz), 7.66 (1H, ddd, J = 0.9Hz, 4.6Hz, 7.3Hz), 8.13 (1H, d, J = 3.7Hz), 8.20 (1H, t, J = 58. 4Hz), 8.52 (1H, dd, J=2.4Hz, 2.4Hz, 7.3Hz), 8.81 (1H, dd, J=2.4Hz, 4.6Hz), 9.30 (1H, dd, J=0.9Hz, 2.4Hz).

(3) 2-(1H-benzo[d]imidazol-1-yl)-7-(difluoromethyl)-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 20-3)
2-chloro-7-(difluoromethyl)-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 20-2) (70.0 mg, 0.249 mmol) in N,N-dimethylformamide (2.5 mL) was added to a solution of benzimidazole (32.0 mg, 0.275 mmol), cesium carbonate (105 mg, 0.325 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (23.8 mg, 50.0 μmol), and tris(dibenzylideneacetone)dipalladium (22.0 mg, 24.0 μmol), and the mixture was heated at 160 ° C. for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration, suspended in methanol, collected by filtration, and dried to obtain the title compound (20-3) (49.0 mg, 0.135 mmol, yield 54%).
^1H -NMR ( _CD3 OD) δ: 7.48 (1H, d, J = 3.7Hz), 7.78 (1H, ddd, J = 0.9Hz, 7.8Hz, 7.9Hz), 7.85 (1H, ddd, J = 0.9 Hz, 7.9Hz, 8.2Hz), 7.95 (1H, dd, J = 0.9Hz, 7.8Hz), 8.18 (1H, d, J = 3.7Hz), 8.30 (1H, t, J = 5 8.4Hz), 8.38 (1H, dd, J=6.4Hz, 8.2Hz), 9.05 (1H, dd, J=0.9Hz, 8.2Hz), 9.12 (1H, dd, J=1. 4Hz, 6.4Hz), 9.55 (1H, ddd, J=1.4Hz, 1.8Hz, 8.2Hz), 9.84 (1H, d, J=1.8Hz), 10.63 (1H, s).

(4) 2-(1H-benzo[d]imidazol-1-yl)-7-(difluoromethyl)-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 20)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-7-(difluoromethyl)-4-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 20-3) (49.0 mg, 0.135 mmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (20) (52.7 mg).
^1H -NMR ( _CD3 OD) δ: 7.48 (1H, d, J = 3.7Hz), 7.80 (1H, ddd, J = 0.9Hz, 7.8Hz, 7.9Hz), 7.86 (1H, ddd, J = 0.9 Hz, 7.9Hz, 8.2Hz), 7.98 (1H, dd, J = 0.9Hz, 7.8Hz), 8.20 (1H, d, J = 3.7Hz), 8.30 (1H, t, J = 5 8.4Hz), 8.39 (1H, dd, J=6.4Hz, 8.2Hz), 9.06 (1H, dd, J=0.9Hz, 8.2Hz), 9.12 (1H, dd, J=1. 4Hz, 6.4Hz), 9.56 (1H, ddd, J=1.4Hz, 1.8Hz, 8.2Hz), 9.86 (1H, d, J=1.8Hz), 10.70 (1H, s).

Compounds (21) and (22) were synthesized from compound (20-1) according to the synthesis method of compound (20).
2-(1H-benzo[d]imidazol-1-yl)-7-(difluoromethyl)-4-(pyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 21)
^1H -NMR ( _CD3 OD) δ: 7.48 (1H, d, J = 4.1Hz), 7.76 (1H, ddd, J = 0.9Hz, 7.7Hz, 7.8Hz), 7.84 (1H, ddd, J = 0.9Hz, 7.7Hz, 8.4Hz), 7.98 (1H, dd, J = 0.9Hz, 7.8Hz), 8.25 (1 H, d, J = 4.1Hz), 8.31 (1H, t, J = 58.6Hz), 8.99 (2H, dd, J = 1.4Hz, 5.5Hz), 9. 04 (1H, dd, J=0.9Hz, 8.4Hz), 9.18 (2H, dd, J=1.4Hz, 5.5Hz), 10.51 (1H, s).

2-(1H-benzo[d]imidazol-1-yl)-7-(difluoromethyl)-4-(2-methylpyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 22)
^1H -NMR ( _CD3 OD) δ: 3.02 (3H, s), 7.50 (1H, d, J = 4.1Hz), 7.75 (1H, dd, J = 8.0Hz, 8.2Hz) , 7.84 (1H, dd, J=8.0Hz, 8.4Hz), 7.98 (1H, d, J=8.2Hz), 8.24 (1H, d, J=4. 1Hz), 8.32 (1H, t, J = 58.6Hz), 8.80 (1H, dd, J = 1.8Hz, 6.0Hz), 8.86 (1H, d , J=1.8Hz), 9.01 (1H, d, J=6.0Hz), 9.04 (1H, d, J=8.2Hz), 10.55 (1H, s).

Example 32
Synthesis of (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methanol hydrochloride (Compound 23)

(1) 7-((benzyloxy)methyl)-2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (Compound 23-1)
To a solution of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (5.81 g, 30.9 mmol) in N,N-dimethylformamide (150 mL), sodium hydride (60% oil dispersion) (1.85 g, 46.3 mmol) and benzyl chloromethyl ether (4.71 mL, 33.9 mmol) were added under ice cooling, and the mixture was then warmed to room temperature and stirred for 1 hour. Water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (23-1) (7.50 g, 24.3 mmol, yield 79%) was obtained from the n-hexane:ethyl acetate (4:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.52 (2H, s), 5.69 (2H, s), 6.65 (1H, d, J = 3.7Hz), 7.25-7.33 (5H, m), 7.38 (1H, d, J = 3.7Hz).

(2) 7-((benzyloxy)methyl)-2-chloro-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 23-2)
To a solution of 7-((benzyloxy)methyl)-2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (compound 23-1) (307 mg, 0.996 mmol) in dimethoxyethane (10 mL), 4-fluorophenylboronic acid (142 mg, 1.01 mmol), potassium carbonate (275 mg, 1.99 mmol), water (1.9 mL), and tetrakis(triphenylphosphine)palladium (57.5 mg, 49.8 μmol) were added, and the mixture was stirred at 80° C. for 1 hour. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in ethyl acetate, collected by filtration, and dried to obtain the title compound (23-2) (360 mg) as a crude product.

(3) 2-(1H-benzo[d]imidazol-1-yl)-7-((benzyloxy)methyl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 23-3)
To a solution of 7-((benzyloxy)methyl)-2-chloro-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 23-2) (360 mg) in N,N-dimethylformamide (10 mL), benzimidazole (138 mg, 1.16 mmol), cesium carbonate (414 mg, 1.27 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (46.6 mg, 97.8 μmol), and tris(dibenzylideneacetone)dipalladium (89.5 mg, 97.8 μmol) were added, and the mixture was heated at 150°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (23-3) (196 mg, 0.436 mmol, two-step yield 44%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 4.67 (2H, s), 5.91 (2H, s), 7.11 (1H, d, J = 3.9Hz), 7.23-7.29 (5H , m), 7.38 (1H, ddd, J=0.9Hz, 7.3Hz, 7.3Hz), 7.45 (1H, ddd, J=0.9Hz, 7.3Hz, 8.2Hz), 7.48-7.53 (2H, m), 7.82 (1H, d, J = 7.3Hz), 7.92 (1H, d, J=3.9Hz), 8.42-8.46 (2H, m), 8.71 (1H, d, J=8.2Hz), 9.36 (1H, s).

(4) (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methanol (Compound 23-4)
Trifluoroacetic acid (3.00 mL, 39.2 mmol) was added to 2-(1H-benzo[d]imidazol-1-yl)-7-((benzyloxy)methyl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 23-3) (30.0 mg, 66.7 μmol), and the mixture was stirred at 100° C. for 1 hour. After cooling, a saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the pH was adjusted to 9, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in dichloromethane, collected by filtration, and dried to obtain the title compound (23-4) (10.1 mg, 28.1 μmol, yield 42%).
^1H -NMR (DMSO- _d6 ) δ: 5.78 (2H, s), 7.09 (1H, d, J = 3.9Hz), 7.42-7.56 (4H, m), 7.84 (1H, d, J = 3.7Hz ), 7.84 (1H, d, J = 7.3Hz), 8.43-8.47 (2H, m), 8.81 (1H, d, J = 7.8Hz), 9.61 (1H, s).

(5) (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methanol hydrochloride (Compound 23)
To a suspension of (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methanol (compound 23-4) (10.1 mg, 28.1 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (23) (5.50 mg).
^1H -NMR (DMSO- _d6 ) δ: 5.90 (2H, s), 7.10 (1H, d, J = 3.9Hz), 7.42-7.56 (4H, m), 7.85 (1H, d, J = 3.7Hz) ), 7.84 (1H, d, J = 7.3Hz), 8.43-8.47 (2H, m), 8.84 (1H, d, J = 7.8Hz), 9.70 (1H, s).

Example 33
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 24)

(1) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 24-1)
To a solution of (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methanol (compound 23-4) (82.5 mg, 0.230 mmol) in tetrahydrofuran (6 mL) was added sodium hydride (60% oil dispersion) (18.3 mg, 0.459 mmol), and the mixture was stirred at room temperature for 20 minutes. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in dichloromethane, collected by filtration, and dried to obtain the title compound (24-1) (59.0 mg, 0.179 mmol, yield 78%).
^1H -NMR (DMSO- _d6 ) δ: 6.97 (1H, d, J = 3.7Hz), 7.34 (1H, dd, J = 7.3Hz, 7.8Hz), 7.43 (1H, dd, J = 7.3Hz, 8.0Hz), 7.43-7.49 (2H, m), 7.68 (1 H, dd, J = 1.8Hz, 3.7Hz), 7.77 (1H, d, J = 7.8Hz), 8.38-8.42 (2H, m), 8.70 (1H, d, J = 8.0Hz), 9.24 (1H, s), 12.47 (1H, s).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 24)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 24-1) (16.0 mg, 48.5 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (24) (15.5 mg).
^1H -NMR (DMSO- _d6 ) δ: 7.04 (1H, d, J = 3.7Hz), 7.45-7.58 (4H, m), 7.77 (1H, d, J = 3.7Hz), 7.86 (1H, d, J=7.8Hz), 8.43-8.48 (2H, m), 8.80 (1H, d, J=7.9Hz), 9.62 (1H, s), 12.67 (1H, s).

Example 34
Synthesis of (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)(phenyl)methanone hydrochloride (Compound 28)

(1) (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)(phenyl)methanone (Compound 28-1)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 24-1) (49.0 mg, 0.149 mmol) in N,N-dimethylformamide (2 mL), sodium hydride (60% oil dispersion) (70.0 mg, 1.75 mmol) and benzoyl chloride (100 μL, 0.868 mmol) were added and stirred at room temperature for 20 minutes. Water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (28-1) (19.0 mg, 43.8 μmol, yield 29%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 7.05 (1H, dd, J=7.3Hz, 7.5Hz), 7.24 (1H, ddd, J=1.4Hz, 8. 2Hz, 8.2Hz), 7.33 (1H, d, J = 4.1Hz), 7.33 (1H, d, J = 7.8Hz), 7. 48 (2H, dd, J = 8.8Hz, 8.8Hz), 7.61-7.67 (3H, m), 7.78-7.94 (3H, m), 8.12 (1H, d, J = 4.1Hz), 8.39-8.42 (2H, m), 9.01 (1H, s).

(2) (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)(phenyl)methanone hydrochloride (Compound 28)
To a suspension of (2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)(phenyl)methanone (compound 28-1) (19.0 mg, 43.8 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (28) (18.5 mg).
^1H -NMR (DMSO- _d6 ) δ: 7.06 (1H, dd, J=7.3Hz, 7.5Hz), 7.26 (1H, ddd, J=1.4Hz, 8. 2Hz, 8.2Hz), 7.33 (1H, d, J = 4.1Hz), 7.33 (1H, d, J = 7.8Hz), 7. 48 (2H, dd, J = 8.8Hz, 8.8Hz), 7.61-7.67 (3H, m), 7.79-7.94 (3H, m), 8.12 (1H, d, J = 4.1Hz), 8.39-8.43 (2H, m), 9.13 (1H, s).

Compound (29) was synthesized from compound (24-1) according to the synthesis method of compound (28).
2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-7-carboxamide hydrochloride (Compound 29)
^1H -NMR (DMSO- _d6 ) δ: 3.33 (6H, s), 7.21 (1H, d, J = 4.1Hz), 7.39 (1H, dd, J = 7.3Hz, 7.8Hz), 7.48-7.54 (3H, m), 7.82 (1H, d, J = 7.8Hz), 7.89 (1H, d, J = 4.1Hz), 8.42-8.45 (2H, m), 8.65 (1H, d, J = 8.2Hz), 9.46 (1H, s).

Example 35
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 84)

(1) 2,4-Dichloro-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 84-1)
To a solution of 2,4-dichloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidine (1.00 g, 4.95 mmol) in N,N-dimethylformamide (10 mL), potassium carbonate (1.05 g, 7.60 mmol) and methyl iodide (0.420 mL, 6.74 mmol) were added under ice cooling, and the mixture was stirred for 2 hours. Water was added to the reaction solution, and the precipitated solid was collected by filtration, washed with acetone, and then dried to obtain the title compound (84-1) (0.724 g, 3.35 mmol, yield 68%).
¹ H-NMR (DMSO-d ₆ ) δ: 2.48 (3H, d, J=1.4Hz), 3.71 (3H, s), 6.48 (1H, d, J=1.4Hz).

(2) 2-chloro-4-(3-methoxyphenyl)-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 84-2)
To a solution of 2,4-dichloro-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 84-1) (130 mg, 0.602 mmol) in dioxane (6 mL), 3-methoxyphenylboronic acid (96.2 mg, 0.632 mmol), 1 M aqueous sodium carbonate solution (1.2 mL, 1.2 mmol), and bis(triphenylphosphine)palladium(II) dichloride (45.5 mg, 64.8 μmol) were added, and the mixture was heated to reflux for 2 hours. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The resulting solid was dissolved in dichloromethane, dried over anhydrous sodium sulfate, and then filtered. The solvent was evaporated under reduced pressure. Furthermore, the organic layer was extracted with diethyl ether, washed with water and saturated brine, dried over anhydrous sodium sulfate, and then filtered. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and a solid was obtained from the n-hexane:ethyl acetate (3:1) fraction. The obtained solid was washed with methanol to obtain the title compound (84-2) (102 mg, 0.354 mmol, yield 59%).
¹ H-NMR (CDCl ₃ ) δ: 2.48 (3H, d, J = 1.0Hz), 3.78 (3H, s), 3.91 (3H, s), 6.56 (1H, d, J = 1.0Hz), 7.05 (1H, ddd, J = 0.9Hz, 2.8Hz, 8.2Hz), 7.43 (1H, dd, J=8.2Hz, 8.2Hz), 7.62-7.64 (1H, m), 7.65-7.68 (1H, m).

(3) 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 84-3)
To a solution of 2-chloro-4-(3-methoxyphenyl)-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 84-2) (96.0 mg, 0.335 mmol) in toluene (3 mL), benzimidazole (47.4 mg, 0.402 mmol), tripotassium phosphate hydrate (107 mg, 0.503 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (16.1 mg, 33.5 μmol), and tris(dibenzylideneacetone)dipalladium (6.10 mg, 6.70 μmol) were added, and the mixture was stirred at 120°C for 2 hours in a sealed reaction vessel. After cooling, chloroform and water were added to the reaction solution, and the precipitated solid was filtered. The filtrate was extracted with chloroform, the organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The resulting solid was purified by silica gel column chromatography (amino silica gel), and the title compound (84-3) (54.8 mg, 0.148 mmol, yield 44%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 2.52 (3H, s), 3.88 (3H, s), 3.95 (3H, s), 6.61 (1H, s), 7.08-7.12 (1H, m), 7.35-7.40 (1H, m), 7.41-7.46 (1H, m), 7.48-7.53 (1H, m), 7.79-7.83 (2H, m), 7.88 (1H, d, J = 8.2Hz), 8.82 (1H, d, J = 7.8Hz), 9.28 (1H, s).

(4) 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 84)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine (compound 84-3) (52.4 mg, 0.142 mmol) in methanol (3 mL), 4 M hydrochloric acid/dioxane solution (0.6 mL) was added and the mixture was stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure, and then diethyl ether was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (84) (32.8 mg).
^1H -NMR ( _CD3 OD) δ: 2.58 (3H, s), 3.92 (3H, s), 3.93 (3H, s), 6.79 (1H, s), 7.16 (1H, dd, J = 2.2Hz, 8.3Hz), 7.53 (1H, dd, J=8.0Hz, 8.0Hz), 7.71-7.86 (4H, m), 7.93 (1H, d, J=8.0Hz), 9.08 (1H, d, J=8.3Hz), 10.36 (1H, s).

Compounds (85) and (86) were synthesized from compound (84-1) according to the synthesis method of compound (84).
2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 85)
^1H -NMR ( _CD3 OD) δ: 2.57 (3H, s), 3.91 (3H, s), 6.81 (1H, d, J = 0.9Hz), 7.34 (2H, dd, J = 8.9Hz, 8.9Hz), 7.71- 7.82 (2H, m), 7.92 (1H, d, J = 8.2Hz), 8.31-8.37 (2H, m), 9.04 (1H, d, J = 8.2Hz), 10.40 (1H, s).

2-(1H-Benzo[d]imidazol-1-yl)-6,7-dimethyl-4-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 86)
^1H -NMR ( _CD3 OD) δ: 2.57 (3H, s), 3.89 (3H, s), 4.04 (3H, s), 6.80 (1H, s), 7.71-7.76 (1H, m), 7.78-7.83 (1 H, m), 7.92 (1H, d, J = 8.2Hz), 8.40 (1H, s), 8.62 (1H, s), 9.07 (1H, d, J = 8.7Hz), 10.39 (1H, s).

Example 36
Synthesis of 6-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine hydrochloride (Compound 12)

(1) 6-chloro-4-(4-fluorophenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (Compound 12-1)
To a solution of 4,6-dichloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (165 mg, 0.807 mmol) in dioxane (8 mL), 4-fluorophenylboronic acid (124 mg, 0.888 mmol), 1 M aqueous sodium carbonate solution (1.60 mL, 1.60 mmol), and bis(triphenylphosphine)palladium(II) dichloride (56.6 mg, 80.7 μmol) were added, and the mixture was stirred at 110° C. for 3 hours. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The solid was suspended in diethyl ether, collected by filtration, and dried to obtain the title compound (12-1) (87.0 mg) as a crude product.

(2) 6-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (Compound 12-2)
To a solution of 6-chloro-4-(4-fluorophenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (Compound 12-1) (87.0 mg) in toluene (3 mL), benzimidazole (47.0 mg, 0.398 mmol), tripotassium phosphate hydrate (114 mg, 0.498 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (16.0 mg, 33.2 μmol), and tris(dibenzylideneacetone)dipalladium (30.4 mg, 33.2 μmol) were added, and the mixture was stirred for 4 hours at 110° C. After cooling, water and n-hexane were added to the reaction solution, and the precipitated solid was collected by filtration. The solid was suspended in methanol, filtered, and dried to obtain the title compound (12-2) (69.0 mg, 0.200 mmol, two-step yield 25%).
^1H -NMR (DMSO- _d6 ) δ: 4.18 (3H, s), 7.41 (1H, dd, J = 7.8Hz, 8.2Hz), 7.49-7.53 (3H, m), 7.83 (1H, d, J=7.8Hz), 8.58-8.62 (2H, m), 8.77 (1H, d, J=8.2Hz), 8.80 (1H, s), 9.46 (1H, s).

(3) 6-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine hydrochloride (Compound 12)
To a suspension of 6-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (compound 12-2) (69.0 mg, 0.200 mmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.4 mL) was added and stirred for 20 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (12) (66.1 mg).
^1H -NMR (DMSO- _d6 ) δ: 4.19 (3H, s), 7.44-7.57 (4H, m), 7.85 (1H, d, J = 7.8Hz), 8.59-8.64 (2H, m), 8.80 (1H, d, J = 8.0Hz), 8.82 (1H, s), 9.61 (1H, s).

Compound (13) was synthesized from 4,6-dichloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidine according to the synthesis method of compound (12).
6-(1H-benzo[d]imidazol-1-yl)-1-methyl-4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride (Compound 13)
^1H -NMR (DMSO- _d6 ) δ: 4.02 (3H, s), 4.14 (3H, s), 7.44 (1H, dd, J = 7.6Hz, 7.7Hz), 7.54 (1H, dd, J = 7.6Hz, 7.9Hz), 7. 83 (1H, d, J = 7.7Hz), 8.66 (1H, s), 8.81 (1H, d, J = 7.9Hz), 8.82 (1H, s), 9.07 (1H, s), 9.62 (1H, s).

Example 37
Synthesis of 5-(6-(1H-benzo[d]imidazol-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine hydrochloride (Compound 91)

(1) 5-(6-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine (Compound 91-1)
To a solution of 4,6-dichloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (150 mg, 0.739 mmol) in dioxane (7 mL), 2-(dimethylamino)pyridine-5-boronic acid (151 mg, 0.909 mmol), 1 M aqueous sodium carbonate solution (1.4 mL, 1.4 mmol), and bis(triphenylphosphine)palladium(II) dichloride (59.5 mg, 84.8 μmol) were added, and the mixture was heated to reflux for 3 hours. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The resulting solid was dissolved in dichloromethane, dried over anhydrous sodium sulfate, and then filtered. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (91-1) (114 mg, 0.395 mmol, 53% yield) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.24 (6H, s), 4.10 (3H, s), 6.66 (1H, d, J = 9.2Hz), 8.33 (1H, s), 8.40 (1H, dd, J = 2.8Hz, 9.2Hz), 9.08 (1H, d, J = 1.8Hz).

(2) 5-(6-(1H-benzo[d]imidazol-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine (Compound 91-2)
To a solution of 5-(6-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine (Compound 91-1) (98.5 mg, 0.341 mmol) in N,N-dimethylformamide (4 mL), benzimidazole (52.4 mg, 0.443 mmol), cesium carbonate (118 mg, 0.362 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (39.8 mg, 83.5 μmol), and tris(dibenzylideneacetone)dipalladium (10.3 mg, 11.2 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The solid was dissolved in a mixed solvent of dichloromethane, methanol, acetone, and dichloromethane, then dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and a solid was obtained from the chloroform:ethyl acetate (2:1) fraction. The obtained solid was suspended in methanol and diethyl ether, then filtered, and dried to obtain the title compound (91-2) (80.6 mg, 0.218 mmol, yield 64%).
¹ H-NMR (CDCl ₃ ) δ: 3.27 (6H, s), 4.20 (3H, s), 6.73 (1H, d, J = 9.2Hz), 7.38-7.43 (1H, m), 7.45-7.50 (1H, m), 7.88 (1H, d, J = 7. 8Hz), 8.36 (1H, s), 8.46 (1H, dd, J = 2.6Hz, 9.0Hz), 8.77 (1H, d, J = 8.2Hz), 9.22 (1H, d, J = 2.2Hz), 9.29 (1H, s).

(3) 5-(6-(1H-benzo[d]imidazol-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine hydrochloride (Compound 91)
To a suspension of 5-(6-(1H-benzo[d]imidazol-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethylpyridin-2-amine (compound 91-2) (80.6 mg, 0.218 mmol) in methanol (4 mL), 4 M hydrochloric acid/dioxane solution (0.4 mL) was added, and the mixture was stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure, and then diethyl ether and methanol were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (91) (70.4 mg).
^1H -NMR ( _CD3 OD) δ: 3.47 (6H, s), 4.28 (3H, s), 7.51 (1H, d, J = 9.6Hz), 7.74-7.79 (1H, m), 7.81-7.86 (1H, m), 7.9 7 (1H, d, J = 8.2Hz), 8.77 (1H, s), 9.01 (1H, dd, J = 2.3Hz, 9.6Hz), 9.03-9.07 (2H, m), 10.64 (1H, s).

Compound (90) was synthesized from 4,6-dichloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidine according to the synthesis method of compound (91).
(4) 3-(6-(1H-benzo[d]imidazol-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethylaniline hydrochloride (Compound 90)
^1H -NMR ( _CD3 OD) δ: 3.45 (6H, s), 4.05 (3H, s), 7.79 (1H, ddd, J = 0.9Hz, 7.8Hz, 7.8Hz), 7.88 (1H, ddd, J = 0.9Hz, 7.3Hz, 8.5Hz), 7. 92-8.04 (3H, m), 8.60-8.65 (1H, m), 8.84 (1H, s), 8.87 (1H, dd, J=1.8Hz, 1.8Hz), 9.10-9.15 (1H, m), 10.71 (1H, s).

Example 38
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)furo[3,2-d]pyrimidine (Compound 42)

(1) 2-chloro-4-(4-fluorophenyl)furo[3,2-d]pyrimidine (Compound 42-1)
To a solution of 2,4-dichlorofuro[3,2-d]pyrimidine (82.4 mg, 0.436 mmol) in dioxane (4.3 mL), 4-fluorophenylboronic acid (58.5 mg, 0.480 mmol), potassium carbonate (90.3 mg, 0.654 mmol), water (0.5 mL), and bis(triphenylphosphine)palladium(II) dichloride (6.10 mg, 8.70 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (42-1) (80.3 mg, 0.323 mmol, yield 74%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 7.01 (1H, d, J = 2.2Hz), 7.24-7.30 (2H, m), 8.10 (1H, d, J = 2.2Hz), 8.52-8.60 (2H, m).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)furo[3,2-d]pyrimidine (Compound 42)
To a solution of 2-chloro-4-(4-fluorophenyl)furo[3,2-d]pyrimidine (compound 42-1) (78.7 mg, 0.293 mmol) in dioxane (3 mL), benzimidazole (36.5 mg, 0.309 mmol), cesium carbonate (143 mg, 0.440 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (14.0 mg, 30.0 μmol), and tris(dibenzylideneacetone)dipalladium (5.40 mg, 5.86 μmol) were added, and the mixture was heated at 180°C for 13 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (42) (47.4 mg, 0.143 mmol, yield 49%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 7.16 (1H, d, J = 2.4Hz), 7.33-7.42 (3H, m), 7.42-7.49 (1H, m), 7.74 (1H, d, J = 8.2 Hz), 8.41 (1H, d, J = 2.4Hz), 8.60-8.66 (2H, m), 8.69 (1H, d, J = 8.2Hz), 9.23 (1H, s).

Example 39
Synthesis of 5-(2-(1H-benzo[d]imidazol-1-yl)furo[3,2-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline hydrochloride (Compound 63)

(1) 5-(2-chlorofuro[3,2-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline (Compound 63-1)
To a solution of 2,4-dichlorofuro[3,2-d]pyrimidine (157 mg, 0.830 mmol) in dioxane (8 mL), 2-fluoro-N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (167 mg, 0.913 mmol), potassium carbonate (173 mg, 1.25 mmol), water (0.8 mL), and bis(triphenylphosphine)palladium(II) dichloride (11.7 mg, 16.6 μmol) were added, and the mixture was heated at 120°C for 1 hour. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (63-1) (214 mg, 0.733 mmol, yield 88%) was obtained from the n-hexane:ethyl acetate (4:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 2.96 (6H, s), 6.99 (1H, d, J=2.4Hz), 7.14-7.22 (1H, m), 8.01-8.09 (3H, m).

(2) 5-(2-(1H-benzo[d]imidazol-1-yl)furo[3,2-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline (Compound 63-2)
To a solution of 5-(2-chlorofuro[3,2-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline (compound 63-1) (195 mg, 0.670 mmol) in toluene (7 mL), benzimidazole (95.0 mg, 0.670 mmol), tripotassium phosphate (214 mg, 1.01 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (32.2 mg, 67.0 μmol), and tris(dibenzylideneacetone)dipalladium (12.3 mg, 13.4 μmol) were added, and the mixture was stirred at 120°C for 8 hours using a sealed reaction vessel. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (63-2) (148 mg, 0.396 mmol, yield 59%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.03 (6H, s), 7.09 (1H, d, J = 2.0Hz), 7.21-7.31 (1H, m), 7.36-7.49 (2H, m), 7.89 (1H, d, J = 7.6Hz), 8.1 3 (1H, d, J = 2.0Hz), 8.13-8.18 (1H, m), 8.22 (1H, dd, J = 2.2Hz, 8.8Hz), 8.78 (1H, d, J = 8.4Hz), 9.22 (1H, s).

(3) 5-(2-(1H-benzo[d]imidazol-1-yl)furo[3,2-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline hydrochloride (Compound 63)
To a suspension of 5-(2-(1H-benzo[d]imidazol-1-yl)furo[3,2-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline (compound 63-2) (148 mg, 0.396 mmol) in methanol (6 mL), 4 M hydrochloric acid/dioxane solution (0.6 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (63) (118.7 mg).
^1H -NMR ( _CD3 OD) δ: 3.31 (6H, s), 7.39-7.44 (1H, m), 7.60-7.69 (1H, m), 7.76-7.83 (1H, m), 7.83-7.90 (1H, m), 7.99 (1 H, d, J = 8.0Hz), 8.64-8.74 (2H, m), 8.83 (1H, dd, J = 2.2Hz, 7.8Hz), 9.10 (1H, d, J = 8.4Hz), 10.63 (1H, s).

Compound (62) was synthesized from 2,4-dichlorofuro[3,2-d]pyrimidine according to the synthesis method of compound (63).
2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)furo[3,2-d]pyrimidine hydrochloride (Compound 62)
^1H -NMR ( _CD3 OD) δ: 3.96 (3H, s), 7.33 (1H, d, J = 2.4Hz), 7.33-7.38 (1H, m), 7.60 (1H, dd, J=7.6Hz, 8.4Hz), 7.70-7.76 (1H, m), 7.77-7.83 (1H, m), 7 94 (1H, d, J=8.0Hz), 8.18-8.21 (1H, m), 8.27 (1H, dd, J=1.0Hz, 7. 8Hz), 8.59 (1H, d, J = 2.0Hz), 9.04 (1H, d, J = 8.0Hz), 10.38 (1H, s).

Example 40
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)furo[3,2-d]pyrimidine hydrochloride (Compound 64)

(1) 2-chloro-4-(1H-imidazol-1-yl)furo[3,2-d]pyrimidine (Compound 64-1)
Imidazole (63.0 mg, 0.926 mmol) and sodium hydride (60% oil dispersion, 60.5 mg, 1.26 mmol) were added to a solution of 2,4-dichlorofuro[3,2-d]pyrimidine (159 mg, 0.842 mmol) in N,N-dimethylformamide (5.5 mL), and the mixture was stirred under ice-cooling for 30 minutes. Water was added to the reaction solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (64-1) (105 mg, 0.478 mmol, yield 57%) was obtained from the n-hexane:ethyl acetate (1:4) fraction.
¹ H-NMR (CDCl ₃ ) δ: 7.07 (1H, d, J = 2.4Hz), 7.28-7.32 (1H, m), 8.06-8.10 (1H, m), 8.14 (1H, d, J = 2.4Hz), 8.77 (1H, s).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)furo[3,2-d]pyrimidine (Compound 64-2)
To a solution of 2-chloro-4-(1H-imidazol-1-yl)furo[3,2-d]pyrimidine (Compound 64-1) (105 mg, 0.478 mmol) in toluene (5.0 mL), benzimidazole (67.8 mg, 0.574 mmol), tripotassium phosphate (152 mg, 0.717 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (23.0 mg, 47.8 μmol), and tris(dibenzylideneacetone)dipalladium (8.8 mg, 9.56 μmol) were added, and the mixture was stirred at 120°C for 6 hours in a sealed reaction vessel. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (64-2) (36.6 mg, 0.121 mmol, yield 25%) was obtained from the n-hexane:ethyl acetate (1:4) fraction.
¹ H-NMR (CDCl ₃ ) δ: 7.16 (1H, d, J = 8.0Hz), 7.36-7.39 (1H, m), 7.40-7.44 (1H, m), 7.46-7.52 (1H, m), 7.89 ( 1H, d, J = 7.6Hz), 8.15-8.20 (2H, m), 8.63 (1H, d, J = 8.0Hz), 8.86-8.89 (1H, m), 9.12 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)furo[3,2-d]pyrimidine hydrochloride (Compound 64)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)furo[3,2-d]pyrimidine (compound 64-2) (36.6 mg, 0.121 mmol) in methanol (3 mL), 4 M hydrochloric acid/dioxane solution (0.3 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to give the title compound (64) (39.8 mg).
^1H -NMR ( _CD3 OD) δ: 7.57 (1H, d, J = 2.0Hz), 7.74-7.81 (1H, m), 7.82-7.88 (1H, m), 7.98 (1H, d, J = 8.0Hz), 8.00-8.04 (1H, m), 8.80 (1H, d, J = 2.0Hz), 8.85-8.90 (1H, m), 9.03 (1H, d, J = 8.8Hz), 10.31 (1H, s), 10.61 (1H, s).

Example 41
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)pyrido[2,3-d]pyrimidine hydrochloride (Compound 5)

(1) 2-chloro-4-(4-fluorophenyl)pyrido[2,3-d]pyrimidine (Compound 5-1)
To a solution of 2,4-dichloropyrido[2,3-d]pyrimidine (250 mg, 1.25 mmol) in dioxane (12 mL), 4-fluorophenylboronic acid (183 mg, 1.31 mmol), 1 M aqueous sodium carbonate solution (2.20 mL, 2.20 mmol), and bis(triphenylphosphine)palladium(II) dichloride (87.7 mg, 0.125 mmol) were added, and the mixture was heated at 140°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (5-1) (301 mg, 1.16 mmol, yield 93%) was obtained from the dichloromethane:methanol (12:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 7.28-7.33 (2H, m), 7.61 (1H, dd, J = 4.3Hz, 8.2Hz), 7.79-7.83 (2 H, m), 8.48 (1H, dd, J=2.1Hz, 8.2Hz), 9.29 (1H, dd, J=2.1Hz, 4.3Hz).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)pyrido[2,3-d]pyrimidine (Compound 5-2)
To a solution of 2-chloro-4-(4-fluorophenyl)pyrido[2,3-d]pyrimidine (compound 5-1) (301 mg, 1.16 mmol) in dioxane (11 mL), benzimidazole (164 mg, 1.39 mmol), cesium carbonate (566 mg, 1.74 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (54.0 mg, 0.116 mmol), and tris(dibenzylideneacetone)dipalladium (21.0 mg, 23.2 μmol) were added, and the mixture was stirred at 110°C for 1 hour. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (5-2) (69.0 mg, 0.202 mmol, yield 17%) was obtained from the n-hexane:ethyl acetate (1:5) fraction.
¹ H-NMR (CDCl ₃ ) δ: 7.35-7.50 (4H, m), 7.56 (1H, dd, J = 4.1Hz, 8.2Hz), 7.86 (1H, d, J = 7.3Hz), 7.90-7.93 (2H, m), 8 .50 (1H, dd, J=1.8Hz, 8.3Hz), 8.90 (1H, d, J=7.3Hz), 9.28 (1H, dd, J=1.8Hz, 4.1Hz), 9.35 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)pyrido[2,3-d]pyrimidine hydrochloride (Compound 5)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)pyrido[2,3-d]pyrimidine (compound 5-2) (69.0 mg, 0.202 mmol) in methanol (6 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (5) (78.0 mg).
^1H -NMR (DMSO- _d6 ) δ: 7.45 (1H, dd, J = 7.3Hz, 8.0Hz), 7.53-7.59 (3H, m), 7.77 (1H, dd, J = 4.4Hz, 8.4Hz), 7.85 (1H, d, J = 8.0Hz), 8.08 -8.12 (2H, m), 8.61 (1H, dd, J = 2.0Hz, 8.4Hz), 8.84 (1H, d, J = 8.0Hz), 9.30 (1H, dd, J = 2.0Hz, 4.4Hz), 9.44 (1H, s).

Compound (6) was synthesized from 2,4-dichloropyrido[2,3-d]pyrimidine according to the synthesis method of compound (5).
2-(1H-benzo[d]imidazol-1-yl)-4-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidine hydrochloride (Compound 6)
^1H -NMR (DMSO- _d6 ) δ: 3.99 (3H, s), 7.42 (1H, dd, J=7.8Hz, 7.8Hz), 7.52 (1H, dd, J= 7.8Hz, 7.8Hz), 7.73 (1H, dd, J = 4.6Hz, 8.7Hz), 7.81 (1H, d, J = 7.8 Hz), 8.57 (1H, s), 8.85 (1H, d, J=7.8Hz), 9.01 (1H, s), 9.03 (1H, d d, J=1.8Hz, 8.7Hz), 9.24 (1H, dd, J=1.8Hz, 4.6Hz), 9.65 (1H, s).

Example 42
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(3,4-dimethoxyphenyl)pyrido[2,3-d]pyrimidine hydrochloride (Compound 50)

(1) 2-chloro-4-(3,4-dimethoxyphenyl)pyrido[2,3-d]pyrimidine (Compound 50-1)
To a solution of 2,4-dichloropyrido[2,3-d]pyrimidine (138 mg, 0.690 mmol) in dioxane (7 mL), 3,4-dimethoxyphenylboronic acid (138 mg, 0.760 mmol), potassium carbonate (143 mg, 1.04 mmol), water (1 mL), and bis(triphenylphosphine)palladium(II) dichloride (9.70 mg, 14.0 μmol) were added, and the mixture was heated at 110°C for 2 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in ethyl acetate and n-hexane, and the insoluble solid was collected by filtration and dried to obtain the title compound (50-1) (141 mg, 0.487 mmol, yield 68%).
¹ H-NMR (DMF-d ₇ ) δ: 3.90-4.10 (6H, m), 7.20-7.30 (1H, m), 7.40-7.50 (2H, m), 7.75-7.90 (1H, m), 8.65-8.75 (1H, m), 9.28-9.36 (1H, m).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(3,4-dimethoxyphenyl)pyrido[2,3-d]pyrimidine (Compound 50-2)
To a solution of 2-chloro-4-(3,4-dimethoxyphenyl)pyrido[2,3-d]pyrimidine (compound 50-1) (141 mg, 0.468 mmol) in toluene (5 mL), benzimidazole (66.4 mg, 0.562 mmol), tripotassium phosphate (199 mg, 0.936 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (22.5 mg, 46.0 μmol), and tris(dibenzylideneacetone)dipalladium (12.9 mg, 14.0 μmol) were added, and the mixture was heated at 120°C for 6 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (50-2) (147 mg, 0.383 mmol, yield 82%) was obtained from the dichloromethane:methanol (100:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.04 (6H, s), 7.13 (1H, d, J = 8.2Hz), 7.39-7.58 (5H, m), 7.86-7.91 (1H, m), 8.62 (1H, dd, J=2.1Hz, 8.2Hz), 8.95 (1H, d, J=7.3Hz), 9.27 (1H, dd, J=2.1Hz, 4.2Hz), 9.38 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-4-(3,4-dimethoxyphenyl)pyrido[2,3-d]pyrimidine hydrochloride (Compound 50)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(3,4-dimethoxyphenyl)pyrido[2,3-d]pyrimidine (compound 50-2) (145 mg, 0.377 mmol) in methanol (8 mL) was added 4 M hydrochloric acid/dioxane solution (0.7 mL), and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (50) (127 mg).
^1H -NMR ( _CD3 OD) δ: 4.01 (6H, s), 7.31 (1H, d, J = 8.2Hz), 7.69 (1H, dd, J = 1.8Hz, 8.2Hz), 7.73 (1H, s), 7.76-7.82 (1H, m), 7.8 4-7.90 (1H, m), 7.96-8.04 (2H, m), 9.10-9.15 (1H, m), 9.28 (1H, d, J = 8.8Hz), 9.41-9.46 (1H, m), 10.58 (1H, s).

Example 43
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one hydrochloride (Compound 54)

(1) 2-(1H-benzo[d]imidazol-1-yl)-5,5-dibromo-4-(4-fluorophenyl)-7-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (Compound 54-1)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 41) (208 mg, 0.549 mmol) in water (2 mL) and tert-butyl alcohol (4.8 mL) was added N-bromosuccinimide (293 mg, 1.65 mmol), and the mixture was stirred at room temperature for 1 hour. Sodium bicarbonate water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (54-1) (304 mg) was obtained as a crude product from the n-hexane:ethyl acetate (1:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 2.51 (3H, s), 7.39-7.53 (2H, m), 7.56-7.64 (2H, m), 7.83 (1H, d, J = 7.8Hz), 8.49-8.54 (2H, m), 8.55 (1H, d, J = 8.0Hz), 9.33 (1H, s).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (Compound 54-2)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-5,5-dibromo-4-(4-fluorophenyl)-7-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (compound 54-1) (303 mg, 0.585 mmol) in tetrahydrofuran (5.8 mL), 2 M aqueous ammonium chloride solution (1.50 mL, 2.93 mmol) and zinc (213 mg, 1.29 mmol) were added and stirred at room temperature for 30 minutes. After filtration through Celite, aqueous sodium bicarbonate solution was added and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (54-2) (34.4 mg, 95.7 μmol, two-step yield 17%) was obtained from the dichloromethane:methanol (100:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 2.57 (3H, s), 4.09 (2H, s), 7.36-7.52 (4H, m), 7.82 (1H, d, J = 7.8Hz), 8.24-8.32 (2H, m), 8.64 (1H, d, J = 8.2Hz), 9.34 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one hydrochloride (Compound 54)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (compound 54-2) (34.4 mg, 95.7 μmol) in methanol (5 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to give the title compound (54) (16.2 mg).
^1H -NMR ( _CD3 OD) δ: 3.44 (3H, s), 4.07 (2H, s), 7.34-7.42 (2H, m), 7.70-7.83 (2H, m), 7.9 4 (1H, d, J = 8.2Hz), 8.23-8.31 (2H, m), 8.96 (1H, d, J = 8.7Hz), 10.36 (1H, s).

Example 44
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidine hydrochloride (Compound 14)

(1) 1,3-Dibenzylpyrimidine-2,4(1H,3H)-dione (Compound 14-1)
Potassium carbonate (29.5 g, 214 mmol) was added to a solution of pyrimidine-2,4(1H,3H)-dione (10.0 g, 89.2 mmol) in N,N-dimethylformamide (350 mL) and stirred at room temperature for 19 hours. After that, benzyl bromide (32.7 mL, 262 mmol) was added and stirred for 2 days. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (14-1) (25.2 g, 86.2 mmol, yield 97%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.96 (2H, s), 5.15 (2H, s), 5.75 (1H, d, J = 8.0Hz), 7.12 (1H, d, J = 8.0Hz), 7.26-7.39 (8H, m), 7.48 (2H, d, J = 6.9Hz).

(2) 1,3-Dibenzyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (Compound 14-2)
To a solution of 1,3-dibenzylpyrimidine-2,4(1H,3H)-dione (compound 14-1) (4.00 g, 13.7 mmol) in diethyl ether (60 mL), sodium hydride (60% oil dispersion) (1.64 g, 41.0 mmol) was added under ice cooling, and then a solution of p-toluenesulfonylmethyl isocyanide (3.98 g, 20.4 mmol) in diethyl ether:dimethyl sulfoxide (4:1) (100 mL) was added dropwise. After completion of the dropwise addition, the mixture was warmed to room temperature and stirred for 15 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (14-2) (2.30 g, 6.94 mmol, yield 51%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 5.04 (2H, s), 5.25 (2H, s), 6.30 (1H, dd, J=2.3Hz, 2.3Hz), 7.21-7.32 (8 H, m), 7.37 (1H, dd, J=2.3Hz, 3.7Hz), 7.49 (2H, d, J=7.3Hz), 8.53 (1H, brs).

(3) 1,3-Dibenzyl-6-methyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (Compound 14-3)
To a solution of 1,3-dibenzyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (compound 14-2) (2.30 g, 6.94 mmol) in N,N-dimethylformamide (23 mL), potassium carbonate (2.87 g, 20.8 mmol) and iodomethane (1.29 mL, 20.8 mmol) were added, and the mixture was stirred at 40°C for 2 hours. After cooling, water was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (14-3) (2.11 g, 6.11 mmol, 88% yield) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.65 (3H, s), 5.00 (2H, s), 5.23 (2H, s), 6.12 (1H, d, J = 2.3Hz), 7.17 (1H, d, J = 2.3Hz), 7.22-7.32 (8H, m), 7.48 (2H, d, J = 6.9Hz).

(4) 6-methyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (Compound 14-4)
Aluminum chloride (2.69 g, 20.2 mmol) was added to a solution of 1,3-dibenzyl-6-methyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (compound 14-3) (1.00 g, 2.89 mmol) in toluene (29 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and then water was added under ice-cooling, followed by stirring for 30 minutes. After dilution with ethyl acetate, the mixture was warmed to room temperature and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in diethyl ether, collected by filtration, and dried to obtain the title compound (14-4) (377 mg, 2.28 mmol, yield 79%).
¹ H-NMR (DMSO-d ₆ ) δ: 3.67 (3H, s), 6.44 (1H, d, J = 1.8Hz), 7.29 (1H, d, J = 1.8Hz), 10.28 (1H, s), 10.36 (1H, s).

(5) 2,4-Dichloro-6-methyl-6H-pyrrolo[3,4-d]pyrimidine (Compound 14-5)
Phosphoryl chloride (4.30 mL, 47.0 mmol) was added to 6-methyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (compound 14-4) (777 mg, 4.70 mmol), and the mixture was heated to 50°C. Diazabicycloundecene (4.20 mL, 28.2 mmol) was then added dropwise, and the mixture was stirred at 80°C for 5 hours. After cooling, ice water was added, and the pH was adjusted to 9 with 2M aqueous sodium hydroxide solution, followed by extraction with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (14-5) (507 mg, 2.51 mmol, yield 53%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.07 (3H, s), 7.25 (1H, d, J=1.8Hz), 7.33 (1H, d, J=1.8Hz).

(6) 2-chloro-4-(4-fluorophenyl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidine (Compound 14-6)
To a solution of 2,4-dichloro-6-methyl-6H-pyrrolo[3,4-d]pyrimidine (compound 14-5) (100 mg, 0.495 mmol) in dioxane (5 mL), 4-fluorophenylboronic acid (72.0 mg, 0.519 mmol), 1 M aqueous sodium carbonate solution (1.00 mL, 1.00 mmol), and bis(triphenylphosphine)palladium(II) dichloride (34.7 mg, 49.5 μmol) were added, and the mixture was stirred at 110° C. for 1 hour. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in diethyl ether, filtered, and dried to obtain the title compound (14-6) (95.0 mg) as a crude product.

(7) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidine (Compound 14-7)
To a solution of 2-chloro-4-(4-fluorophenyl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidine (compound 14-6) (95.0 mg) in toluene (3 mL), benzimidazole (51.0 mg, 0.436 mmol), tripotassium phosphate hydrate (125 mg, 0.545 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (17.5 mg, 36.3 μmol), and tris(dibenzylideneacetone)dipalladium (33.2 mg, 36.3 μmol) were added, and the mixture was stirred at 110°C for 2 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (14-7) (60.0 mg, 0.174 mmol, two-step yield 35%) was obtained from the n-hexane:ethyl acetate (1:1) fraction.
^1H -NMR (DMSO- _d6 ) δ: 4.13 (3H, s), 7.36 (1H, dd, J = 7.3Hz, 7.8Hz), 7.46 (1H, dd, J = 7.8Hz, 8.2Hz), 7.48-7.53 (2H, m), 7.69 (1H, d, J=1.8Hz), 7.79 (1H, d, J=7.3Hz), 8.13 (1H, d, J=1.8Hz), 8.46-8.50 (2H, m), 9.72 (1H, d, J=8.2Hz), 9.32 (1H, s).

(8) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidine hydrochloride (Compound 14)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidine (Compound 14-7) (60.0 mg, 0.174 mmol) in methanol (2.5 mL), 4 M hydrochloric acid/dioxane solution (0.4 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (14) (57.6 mg).
^1H -NMR ( _CD3 OD) δ: 4.21 (3H, s), 7.38-7.43 (2H, m), 7.68 (1H, d, J = 1.8Hz), 7.73 (1H, dd, J = 7.3Hz, 8.2Hz), 7.78 (1H, dd, J = 7.3H z, 8.2Hz), 7.92 (1H, d, J = 8.2Hz), 8.02 (1H, d, J = 1.8Hz), 8.44-8.48 (2H, m), 9.11 (1H, d, J = 8.2Hz), 10.40 (1H, s).

Compound (15) was synthesized from compound (14-5) according to the synthesis method of compound (14).
5-(2-(1H-benzo[d]imidazol-1-yl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline hydrochloride (Compound 15)
^1H -NMR (DMSO- _d6 ) δ: 3.28 (6H, s), 4.24 (3H, s), 7.58 (1H, dd, J = 8.7Hz, 11.5Hz), 7.75 (1H, d, J = 1.8Hz), 7.77-7.83 (2H, m), 7.95 (1H, d, J = 8.2Hz), 8.08 (1H, d, J = 1.8Hz), 8.31-8.35 (1H, m), 8.48 (1H, d, J = 7.8Hz), 9.14 (1H, d, J = 8.2Hz), 9.55 (1H, s).

Compound (16) was synthesized from compound (14-5) according to the synthesis method of compound (64) from 2,4-dichlorofuro[3,2-d]pyrimidine.
2-(1H-benzo[d]imidazol-1-yl)-4-(1H-imidazol-1-yl)-6-methyl-6H-pyrrolo[3,4-d]pyrimidine hydrochloride (Compound 16)
^1H -NMR (DMSO- _d6 ) δ: 4.16 (3H, s), 7.45 (1H, dd, J = 7.7Hz, 7.9Hz), 7.54 (1H, dd, J = 7.7Hz, 8.3Hz), 7.83 (1H, s), 7.84 (1H, d, J=1.7Hz), 7.84 (1H, d, J=7.9Hz), 8.41 (1H, d, J=1.7Hz), 8.66 (1H, s), 8.75 (1H, d, J=8.3Hz), 9.74 (2H, s).

Example 45
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)thieno[3,4-d]pyrimidine hydrochloride (Compound 55)

(1) Methyl 4-ureidothiophene-3-carboxylate (Compound 55-1)
To methyl 4-aminothiophene-3-carboxylate (2.08 g, 13.2 mmol), 50% aqueous acetic acid (50 mL), water (17 mL), and sodium cyanate (1.72 g, 26.5 mmol) were added, and the mixture was stirred at room temperature for 24 hours. The reaction solution was concentrated under reduced pressure by azeotropy with toluene, and then 2 M hydrochloric acid was added, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in chloroform and n-hexane, and the insoluble solid was collected by filtration and dried to obtain the title compound (55-1) (1.68 g, 8.38 mmol, yield 63%).
¹ H-NMR (DMSO-d ₆ ) δ: 3.84 (3H, s), 6.04-6.06 (2H, brs), 7,66 (1H, d, J = 3.7Hz), 8.29 (1H, d, J = 3.7Hz), 8.91 (1H, s).

(2) Thieno[3,4-d]pyrimidine-2,4(1H,3H)-dione (Compound 55-2)
To a solution of methyl 4-ureidothiophene-3-carboxylate (compound 55-1) (3.00 g, 15.0 mmol) in ethanol (65 mL), a 21 wt. % sodium ethoxide/ethanol solution (12.2 mL, 37.5 mmol) was added and stirred at room temperature for 4 hours. The undissolved solid in the reaction solution was collected by filtration and dried to obtain the title compound (55-2) (2.80 g) as a crude product.
¹ H-NMR (DMSO-d ₆ ) δ: 6.39 (1H, d, J=3.2Hz), 7.89 (1H, d, J=3.2Hz).

(3) 2,4-Dichlorothieno[3,4-d]pyrimidine (Compound 55-3)
Phosphoryl chloride (24.0 mL, 0.257 mol) was added to a solution of thieno[3,4-d]pyrimidine-2,4(1H,3H)-dione (compound 55-2) (2.43 g, 14.4 mmol) in N,N-dimethylaniline (4.8 mL), and the mixture was heated at 100°C for 1 hour. After cooling, the solvent was evaporated under reduced pressure, and aqueous sodium bicarbonate was added, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (55-3) (730 mg, 3.56 mmol, two-step yield 24%) was obtained from the dichloromethane:methanol (30:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 7.96 (1H, d, J=3.2Hz), 8.30 (1H, d, J=3.2Hz).

(4) 2-chloro-4-(3-methoxyphenyl)thieno[3,4-d]pyrimidine (compound 55-4)
To a solution of 2,4-dichlorothieno[3,4-d]pyrimidine (compound 55-3) (109 mg, 0.529 mmol) in dioxane (5 mL), 3-methoxyphenylboronic acid (88.5 mg, 0.582 mmol), potassium carbonate (110 mg, 0.794 mmol), water (0.8 mL), and bis(triphenylphosphine)palladium(II) dichloride (7.43 mg, 10.6 μmol) were added, and the mixture was heated at 110°C for 2 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (55-4) (147 mg, 0.533 mmol, 100% yield) was obtained from the n-hexane:ethyl acetate (4:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.93 (3H, s), 7.14-7.19 (1H, m), 7.51 (1H, dd, J = 7.8Hz, 7.8Hz), 7.56 (1H, dd, J =2.0Hz, 4.0Hz), 7.61-7.65 (1H, m), 7.93 (1H, d, J = 3.5Hz), 8.33 (1H, d, J = 3.5Hz).

(5) 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)thieno[3,4-d]pyrimidine (Compound 55-5)
A solution of 2-chloro-4-(3-methoxyphenyl)thieno[3,4-d]pyrimidine (compound 55-4) (145 mg, 0.524 mmol) in toluene (5.3 mL) was placed in a sealed reaction vessel, and benzimidazole (74.3 mg, 0.629 mmol), tripotassium phosphate (222 mg, 1.05 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl (25.2 mg, 52.4 μmol), and tris(dibenzylideneacetone)dipalladium (14.4 mg, 16.0 μmol) were added, followed by heating at 120°C for 8 hours. After cooling, water was added to the reaction solution, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (55-5) (88.1 mg, 0.246 mmol, yield 47%) was obtained from the n-hexane:ethyl acetate (4:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.97 (3H, s), 7.20-7.25 (1H, m), 7.38-7.50 (2H, m), 7.58 (1H, dd, J = 7.8Hz, 7.8Hz), 7.68 (1H, dd, J = 2.2Hz, 4.4Hz), 7. 72-7.76 (1H, m), 7.89 (1H, d, J = 8.2Hz), 7.93 (1H, d, J = 3.5Hz), 8.37 (1H, d, J = 3.5Hz), 8.85 (1H, d, J = 7.8Hz), 9.29 (1H, s).

(6) 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)thieno[3,4-d]pyrimidine hydrochloride (Compound 55)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(3-methoxyphenyl)thieno[3,4-d]pyrimidine (compound 55-5) (86.3 mg, 0.241 mmol) in methanol (6 mL), 4 M hydrochloric acid/dioxane solution (0.6 mL) was added and the mixture was stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (55) (71.0 mg).
^1H -NMR ( _CD3 OD) δ: 3.96 (3H, s), 7.28-7.33 (1H, m), 7.62 (1H, dd, J = 7.6Hz, 8.4Hz), 7.71-7.88 (4H, m), 7.94 (1H , d, J=7.6Hz), 8.35 (1H, d, J=3.0Hz), 8.83 (1H, d, J=3.0Hz), 9.15 (1H, d, J=7.8Hz), 10.41 (1H, s).

Compounds (56) and (57) were synthesized from compound (55-3) according to the synthesis method of compound (55).
5-(2-(1H-benzo[d]imidazol-1-yl)thieno[3,4-d]pyrimidin-4-yl)-2-fluoro-N,N-dimethylaniline hydrochloride (Compound 56)
^1H -NMR ( _CD3 OD) δ: 3.38 (6H, s), 7.65-7.72 (1H, m), 7.75-7.89 (2H, m), 7.98 (1H, d, J = 8.0Hz), 8.33-8.41 (1H, m), 8 .45 (1H, d, J = 3.2Hz), 8.52-8.60 (1H, m), 8.95 (1H, d, J = 3.2Hz), 9.18 (1H, d, J = 8.8Hz), 10.63 (1H, s).

2-(1H-benzo[d]imidazol-1-yl)-4-(1-methyl-1H-pyrazol-4-yl)thieno[3,4-d]pyrimidine hydrochloride (Compound 57)
^1H -NMR ( _CD3 OD) δ: 4.08 (3H, s), 7.69-7.83 (2H, m), 7.91 (1H, d, J = 8.0Hz), 8.22 (1H, d, J = 3.2Hz), 8 .64 (1H, s), 8.92 (1H, s), 8.96 (1H, d, J = 3.2Hz), 9.11 (1H, d, J = 8.2Hz), 10.45 (1H, s).

Example 46
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine hydrochloride (Compound 2)

(1) tert-butyl 2-chloro-4-(4-fluorophenyl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (Compound 2-1)
To a solution of tert-butyl 2,4-dichloro-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (300 mg, 1.03 mmol) in dioxane (10 mL), 4-fluorophenylboronic acid (144 mg, 1.03 mmol), 1 M aqueous sodium carbonate solution (2.00 mL, 2.00 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (42.0 mg, 51.4 μmol) were added, and the mixture was heated at 140°C for 10 minutes using a microwave synthesizer. Water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (2-1) (203 mg, 0.581 mmol, yield 56%) was obtained from the n-hexane:ethyl acetate (3:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.51 (9H, s), 4.89 (2H, s), 4.92 (2H, s), 7.18-7.28 (2H, m), 7.95-7.98 (2H, m).

(2) tert-butyl 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (Compound 2-2)
To a solution of tert-butyl 2-chloro-4-(4-fluorophenyl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (Compound 2-1) (200 mg, 0.573 mmol) in dioxane (6 mL), benzimidazole (81.0 mg, 0.687 mmol), cesium carbonate (279 mg, 0.859 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (27.3 mg, 57.3 μmol), and tris(dibenzylideneacetone)dipalladium (52.5 mg, 57.3 μmol) were added, and the mixture was heated at 150°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The solid was purified by silica gel column chromatography, and the title compound (2-2) (192 mg, 0.445 mmol, yield 78%) was obtained from the n-hexane:ethyl acetate (1:10) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.47 (9H, s), 4.79 (2H, s), 5.01 (2H, s), 7.20-7.35 (4H, m), 7.86 (1 H, d, J = 7.3Hz), 8.01-8.08 (2H, m), 8.60 (1H, d, J = 7.3Hz), 9.13 (1H, s).

(3) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine hydrochloride (Compound 2)
To a suspension of tert-butyl 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (Compound 2-2) (24.0 mg, 55.6 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (2 mL) was added and the mixture was stirred at 40° C. for 30 minutes. After allowing to cool, the solvent was evaporated under reduced pressure. Dichloromethane was added to the residue, and the resulting solid was collected by filtration and dried to obtain the title compound (2) (8.00 mg).
^1H -NMR ( _CD3 OD) δ: 4.89 (2H, s), 5.08 (2H, s), 7.41-7.63 (4H, m), 7.86 (1H, d, J = 7.8Hz), 8.17-8.20 (2H, m), 8.79 (1H, d, J = 8.2Hz), 9.84 (1H, s).

Example 47
Synthesis of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine hydrochloride (Compound 3)

(1) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine (Compound 3-1)
To a solution of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine hydrochloride (Compound 2) (49.0 mg) in dichloromethane (2 mL), triethylamine (30.0 μL, 220 μmol), acetic acid (12.0 μL, 220 μmol), 37% aqueous formaldehyde solution (16.0 μL, 161 μmol), and sodium triacetoxyborohydride (34.0 mg, 165 μmol) were added and stirred at room temperature for 50 minutes. Water was added to the reaction solution, which was then extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (3-1) (19.0 mg, 55.0 μmol) was obtained from the dichloromethane:methanol (10:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 2.70 (3H, s), 4.06 (2H, s), 4.24 (2H, s), 7.24-7.43 (4H, m), 7.83 (1 H, d, J = 7.8Hz), 7.96-8.00 (2H, m), 8.62 (1H, d, J = 8.2Hz), 9.15 (1H, s).

(2) 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine hydrochloride (Compound 3)
To a suspension of 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine (compound 3-1) (19.0 mg, 55.0 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (3) (19.1 mg).
^1H -NMR ( _CD3 OD) δ: 2.89 (3H, s), 5.22 (2H, s), 5,24 (2H, s), 7.44-7.48 (2H, m), 7.66 (1H, dd, J = 7.3Hz, 7.3Hz), 7.71 (1 H, dd, J = 7.3Hz, 7.8Hz), 7.92 (1H, d, J = 7.3Hz), 8.18-8.21 (2H, m), 8.85 (1H, d, J = 7.8Hz), 10.09 (1H, s).

Example 48
Synthesis of 1-(2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)ethanone hydrochloride (Compound 4)

(1) 1-(2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)ethanone (Compound 4-1)
Triethylamine (1.00 mL, 7.17 mmol) and acetic anhydride (800 μL, 8.46 mmol) were added to 2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine hydrochloride (compound 2) (102 mg), and the mixture was stirred at room temperature for 40 minutes. Water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (4-1) (44.3 mg, 0.118 mmol) was obtained from the dichloromethane:methanol (10:1) fraction.
^1H -NMR ( _CD3 OD) δ: 2.26 (3H, s), 5.10 (2H, s), 5.11 (2H, s), 7.39-7.44 (2H, m), 7.74 (1H, dd, J = 7.3Hz, 7.3Hz), 7.82 (1 H, dd, J = 7.3Hz, 8.2Hz), 7.97 (1H, d, J = 7.3Hz), 8.28-8.31 (2H, m), 8.95 (1H, d, J = 8.2Hz), 10.33 (1H, s).

(2) 1-(2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)ethanone hydrochloride (Compound 4)
To a suspension of 1-(2-(1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)ethanone (compound 4-1) (44.3 mg, 0.118 mmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.5 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (4) (37.1 mg).
^1H -NMR ( _CD3 OD) δ: 2.28 (3H, s), 5.11 (2H, s), 5.12 (2H, s), 7.41-7.46 (2H, m), 7.74 (1H, dd, J = 7.3Hz, 7.3Hz), 7.83 (1 H, dd, J = 7.3Hz, 8.2Hz), 7.97 (1H, d, J = 7.3Hz), 8.28-8.31 (2H, m), 8.97 (1H, d, J = 8.2Hz), 10.54 (1H, s).

Example 49
Synthesis of 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-5-ol hydrochloride (Compound 19)

(1) 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 19-1)
To a solution of 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 1-1) (800 mg, 3.96 mmol) in dioxane (16 mL), 4-fluorophenylboronic acid (554 mg, 3.96 mmol), 1 M aqueous sodium carbonate solution (3.20 mL, 3.20 mmol), and bis(triphenylphosphine)palladium(II) dichloride (278 mg, 0.396 μmol) were added, and the mixture was stirred under reflux for 1 hour. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (19-1) (900 mg, 3.44 mmol, 87% yield) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.88 (3H, s), 6.77 (1H, d, J=3.7Hz), 7.20-7.25 (3H, m), 8.11-8.14 (2H, m).

(2) 4-(4-fluorophenyl)-N-(4-methoxy-2-nitrophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine (Compound 19-2)
4-Methoxy-2-nitroaniline (124 mg, 0.738 mmol), cesium carbonate (297 mg, 0.914 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (66.0 mg, 139 μmol), and tris(dibenzylideneacetone)dipalladium (64.0 mg, 69.9 μmol) were added to a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 19-1) (152 mg, 0.703 mmol) in N,N-dimethylformamide (5 mL), and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration, suspended in diethyl ether, and then collected by filtration and dried to obtain the title compound (19-2) (218 mg, 0.554 mmol, yield 79%).
¹ H-NMR (CDCl ₃ ) δ: 3.67 (3H, s), 3.81 (3H, s), 6.72 (1H, d, J=3.7Hz), 7.34-7.42 (4H, m), 7. 54 (1H, d, J = 2.8Hz), 8.12-8.16 (2H, m), 8.21 (1H, d, J = 9.2Hz), 9.88 (1H, s).

(3) N ¹ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-4-methoxybenzene-1,2-diamine (Compound 19-3)
Palladium-activated carbon (Pd 10%) (1.00 g, 0.939 mmol) was added to a solution of 4-(4-fluorophenyl)-N-(4-methoxy-2-nitrophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine (compound 19-2) (218 mg, 0.554 mmol) in methanol (10 mL), and the mixture was stirred at room temperature under a hydrogen gas atmosphere for 14 hours. The reaction solution was filtered through Celite, and the filtrate was concentrated under reduced pressure. Diethyl ether was added to the residue, and the precipitated solid was collected by filtration and dried to obtain the title compound (19-3) (128 mg) as a crude product.

(4) 4-(4-fluorophenyl)-2-(5-methoxy-1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 19-4)
To a solution of N ¹ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-4-methoxybenzene-1,2-diamine (compound 19-3) (128 mg) in dioxane (4 mL), triethyl orthoformate (0.232 mL, 1.76 mmol) and p-toluenesulfonic acid (18.0 mg, 0.104 mmol) were added, and the mixture was heated at 130°C for 10 minutes using a microwave synthesis system. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in methanol, collected by filtration, and dried to obtain the title compound (19-4) (100 mg, 0.268 mmol, two-step yield 48%).
^1H -NMR (DMSO- _d6 ) δ: 3.85 (3H, s), 3.96 (3H, s), 7.02 (1H, d, J = 3.7Hz), 7.09 (1H, dd, J = 2.3Hz, 8.7Hz), 7.34 (1H, d, J = 2.3 Hz), 7.46-7.50 (2H, m), 7.73 (1H, d, J = 3.7Hz), 8.41-8.44 (2H, m), 8.63 (1H, d, J = 8.7Hz), 9.31 (1H, s).

(5) 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-5-ol (Compound 19-5)
To a solution of 4-(4-fluorophenyl)-2-(5-methoxy-1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 19-4) (100 mg, 0.268 mmol) in dichloromethane (4 mL), 1 M boron tribromide/dichloromethane solution (2.00 mL, 2.00 mmol) was added dropwise under ice cooling, and the mixture was then warmed to room temperature and stirred for 1 hour. Water and n-hexane were added to the reaction mixture, and the precipitated solid was collected by filtration. The solid was suspended in acetone, collected by filtration, and dried to obtain the title compound (19-5) (82.0 mg, 0.228 mmol, yield 85%).
^1H -NMR (DMSO- _d6 ) δ: 3.99 (3H, s), 4.13 (1H, brs), 7.10 (1H, d, J=3.7Hz), 7.13 (1H, dd, J=2.3Hz, 8.7Hz), 7.17 (1H, d, J=2. 3Hz), 7.47-7.52 (2H, m), 7.83 (1H, d, J = 3.7Hz), 8.44-8.47 (2H, m), 8.69 (1H, d, J = 8.7Hz), 10.02 (1H, s).

(6) 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-5-ol hydrochloride (Compound 19)
To a suspension of 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-5-ol (compound 19-5) (82.0 mg, 0.228 mmol) in methanol (5 mL), 4 M hydrochloric acid/dioxane solution (2 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then dichloromethane was added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (19) (76.0 mg).
^1H -NMR ( _CD3 OD) δ: 4.04 (3H, s), 7.07 (1H, d, J = 3.7Hz), 7.20 (1H, d, J = 2.3Hz), 7.25 (1H, dd, J = 2.3Hz, 9.2Hz), 7 .37-7.41 (2H, m), 7.66 (1H, d, J = 3.7Hz), 8.38-8.42 (2H, m), 8.87 (1H, d, J = 9.2Hz), 10.21 (1H, s).

Example 50
Synthesis of methyl 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazole-4-carboxylate hydrochloride (Compound 73)

(1) Methyl 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazole-4-carboxylate (Compound 73-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 19-1) (301 mg, 1.15 mmol) in N,N-dimethylformamide (11 mL), methyl 1H-benzo[d]imidazole-4-carboxylate (243 mg, 1.38 mmol), cesium carbonate (564 mg, 1.73 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (110 mg, 230 μmol), and tris(dibenzylideneacetone)dipalladium (52.7 mg, 57.5 μmol) were added, and the mixture was heated at 160°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography, and the title compound (73-1) (96.6 mg, 0.241 mmol, yield 21%) was obtained from the dichloromethane:methanol (40:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.00 (3H, s), 4.10 (3H, s), 6.85 (1H, d, J = 3.2Hz), 7.24-7.36 (3H, m), 7.51 (1H, dd, J = 7.6H z, 8.4Hz), 8.06-8.12 (1H, m), 8.21-8.29 (2H, m), 9.06 (1H, dd, J=1.2Hz, 8.0Hz), 9.39 (1H, s).

(2) Methyl 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazole-4-carboxylate hydrochloride (Compound 73)
To a suspension of methyl 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazole-4-carboxylate (compound 73-1) (35.8 mg, 8.92 μmol) in methanol (3 mL), 4 M hydrochloric acid/dioxane solution (0.3 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (73) (31.2 mg).
^1H -NMR ( _CD3 OD) δ: 4.06 (3H, s), 4.13 (3H, s), 7.10 (1H, d, J=3.6Hz), 7.33-7.45 (2H, m), 7.69-7. 76 (1H, m), 7.90-8.00 (1H, m), 8.34-8.47 (3H, m), 9.33-9.43 (1H, m), 10.52 (1H, s).

Compound (75) was synthesized from compound (19-1) according to the synthesis method of compound (73).
1-(1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-4-yl)ethan-1-one hydrochloride (Compound 75)
^1H -NMR ( _CD3 OD) δ: 2.83 (3H, s), 3.99-4.07 (3H, m), 7.01-7.10 (1H, m), 7.28-7.42 (2H, m), 7.63-7 .74 (1H, m), 7.92-8.04 (1H, m), 8.29-8.48 (3H, m), 9.27-9.39 (1H, m), 10.46 (1H, s).

Example 51
Synthesis of 2-(4-ethyl-1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 74)

(1) 4-(4-fluorophenyl)-7-methyl-2-(4-vinyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 74-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 19-1) (48.9 mg, 0.187 mmol) in N,N-dimethylformamide (2 mL), 4-vinyl-1H-benzo[d]imidazole (32.4 mg, 0.224 mmol), cesium carbonate (91.6 mg, 0.281 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (17.8 mg, 37.4 μmol), and tris(dibenzylideneacetone)dipalladium (8.6 mg, 9.35 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by preparative TLC (preparative thin layer chromatography) (amino silica gel), and the title compound (74-1) (49.1 mg, 0.133 mmol, yield 71%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.99 (3H, s), 5.54 (1H, d, J = 10.0Hz), 6.30 (1H, d, J = 18.0Hz), 6.82 (1H, d, J = 3.6Hz), 7.20-7. 33 (3H, m), 7.35-7.54 (3H, m), 8.25 (2H, dd, J = 5.4Hz, 8.6Hz), 8.71 (1H, d, J = 8.4Hz), 9.28 (1H, s).

(2) 2-(4-ethyl-1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 74-2)
Palladium-activated carbon (Pd 10%) (3.9 mg) was added to a mixed solution of 4-(4-fluorophenyl)-7-methyl-2-(4-vinyl-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (compound 74-1) (19.5 mg, 52.8 μmol) in methanol (3 mL) and dichloromethane (3 mL), and the mixture was stirred at room temperature under a hydrogen gas atmosphere for 16 hours. The reaction mixture was filtered through Celite, and the resulting filtrate was evaporated under reduced pressure. The residue was purified by preparative thin-layer chromatography (TLC), and the title compound (74-2) (12.4 mg, 33.4 μmol, yield 63%) was obtained from the n-hexane:ethyl acetate (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.44 (3H, t, J = 7.6Hz), 3.18 (2H, q, J = 7.6Hz), 3.95 (3H, s), 6.79 (1H, d, J = 3.6Hz), 7.18-7.24 (2H, m), 7.24 -7.33 (2H, m), 7.38 (1H, dd, J = 7.6Hz, 7.8Hz), 8.19-8.28 (2H, m), 8.61 (1H, dd, J = 0.8Hz, 8.4Hz), 9.22 (1H, s).

(3) 2-(4-ethyl-1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 74)
To a suspension of 2-(4-ethyl-1H-benzo[d]imidazol-1-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 74-2) (12.4 mg, 33.4 μmol) in methanol (1 mL), 4 M hydrochloric acid/dioxane solution (0.1 mL) was added and the mixture was stirred at room temperature for 10 minutes. After the solvent was evaporated under reduced pressure, ethyl acetate and n-hexane were added to the residue, and the resulting solid was collected by filtration and dried to give the title compound (74) (9.6 mg).
^1H -NMR ( _CD3 OD) δ: 1.44 (3H, t, J = 7.6Hz), 3.12 (2H, q, J = 7.6Hz), 4.05 (3H, s), 7.08 (1H, d, J = 4.0Hz), 7.34-7.43 (2H, m), 7.58 (1 H, d, J = 7.2Hz), 7.69 (1H, d, J = 3.6Hz), 7.71-7.77 (1H, m), 8.38-8.47 (2H, m), 8.93 (1H, d, J = 8.4Hz), 10.46 (1H, s).

Example 52
Synthesis of 4-(4-fluorophenyl)-2-(4-(methoxymethyl)-1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 79)

(1) (1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-4-yl)methanol (Compound 79-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 19-1) (334 mg, 1.28 mmol) in N,N-dimethylformamide (10 mL), (1H-benzo[d]imidazol-4-yl)methanol (228 mg, 1.54 mmol), cesium carbonate (626 mg, 1.92 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (122 mg, 0.256 mmol), and tris(dibenzylideneacetone)dipalladium (58.6 mg, 64.0 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography (amino silica gel), and the title compound (79-1) (54.8 mg, 0.147 mmol, yield 11%) was obtained from the dichloromethane:methanol (50:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.99 (3H, s), 5.20 (2H, d, J = 6.4Hz), 6.83 (1H, d, J = 4.0Hz), 7.23-7.36 (4H, m), 7.39-7.48 (1H, m), 8.21-8.31 (2H, m), 8.71 (1H, d, J=8.4Hz), 9.26 (1H, s).

(2) 4-(4-fluorophenyl)-2-(4-(methoxymethyl)-1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 79-2)
To a solution of (1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-4-yl)methanol (Compound 79-1) (28.2 mg, 75.5 μmol) in N,N-dimethylformamide (1.5 mL), methyl iodide (94 μL, 0.151 mmol) and sodium hydride (60% oil dispersion) (7.2 mg, 0.151 mmol) were added, and the mixture was stirred under ice-cooling for 3 hours. Water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (79-2) (29.0 mg, 74.9 μmol, yield 99%) was obtained from the dichloromethane:ethyl acetate (10:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.54 (3H, s), 3.99 (3H, s), 5.04 (2H, s), 6.83 (1H, d, J = 3.6Hz), 7.22-7.35 ( 3H, m), 7.41-7.50 (2H, m), 8.21-8.29 (2H, m), 8.70-8.78 (1H, m), 9.26 (1H, s).

(3) 4-(4-fluorophenyl)-2-(4-(methoxymethyl)-1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 79)
To a suspension of 4-(4-fluorophenyl)-2-(4-(methoxymethyl)-1H-benzo[d]imidazol-1-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 79-2) (29.0 mg, 74.9 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.2 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and diethyl ether were added to the residue. The resulting solid was collected by filtration and dried to give the title compound (79) (19.4 mg).
^1H -NMR ( _CD3 OD) δ: 3.52 (3H, s), 4.06 (3H, s), 4.94 (2H, s), 7.08 (1H, d, J = 3.6Hz), 7.39 (2H, dd, J = 8.8Hz, 9.2Hz ), 7.64-7.72 (2H, m), 7.74-7.81 (1H, m), 8.38-8.46 (2H, m), 9.06 (1H, d, J = 8.4Hz), 10.41 (1H, s).

Example 53
Synthesis of 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-b]pyridine hydrochloride (Compound 65)

(1) 4-(4-fluorophenyl)-7-methyl-N-(2-nitropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (Compound 65-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 19-1) (210 mg, 0.804 mmol) in N,N-dimethylformamide (5 mL), 3-amino-2-nitropyridine (134 mg, 0.965 mmol), cesium carbonate (394 mg, 1.21 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (76.8 mg, 161 μmol), and tris(dibenzylideneacetone)dipalladium (36.8 mg, 40.2 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography, and the title compound (65-1) (105 mg, 0.287 mmol, yield 36%) was obtained from the dichloromethane:methanol (25:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.87 (3H, s), 6.73 (1H, d, J = 4.0Hz), 7.12 (1H, d, J = 3.6Hz), 7.22-7.31 (2H, m), 7 .60-7.68 (1H, m), 8.11-8.21 (3H, m), 9.79 (1H, dd, J=1.2Hz, 8.8Hz), 10.34 (1H, s).

(2) N ³ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyridine-2,3-diamine (Compound 65-2)
Palladium-activated carbon (Pd 10%) (20.9 mg, 19.6 μmol) was added to a solution of 4-(4-fluorophenyl)-7-methyl-N-(2-nitropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (compound 65-1) (105 mg, 0.287 mmol) in ethanol (3 mL), and the mixture was stirred at room temperature under a hydrogen gas atmosphere for 16 hours. The reaction solution was filtered through Celite, and the resulting filtrate was evaporated under reduced pressure to give the title compound (65-2) (102 mg) as a crude product.
¹ H-NMR (CDCl ₃ ) δ: 3.75 (3H, s), 4.68 (2H, brs), 6.58-6.62 (2H, m), 6.79 (1H, dd, J=5.0Hz, 7.8Hz) , 6.97 (1H, d, J=3.6Hz), 7.17-7.24 (2H, m), 7.93-8.00 (2H, m), 8.06-8.13 (2H, m).

(3) 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-b]pyridine (Compound 65-3)
To a solution of N ³ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyridine-2,3-diamine (Compound 65-2) (102 mg, 0.304 mmol) in dioxane (3 mL), triethyl orthoformate (0.253 mL, 1.52 mmol) and p-toluenesulfonic acid monohydrate (17.3 mg, 91.2 μmol) were added, and the mixture was heated at 130°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was subjected to preparative thin layer chromatography (TLC), and the title compound (65-3) (31.8 mg, 92.3 μmol, two-step yield 30%) was obtained from the ethyl acetate:methanol (10:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.00 (3H, s), 6.85 (1H, d, J = 3.6Hz), 7.23-7.42 (4H, m), 8.24 (2H, dd, J = 5.4Hz, 8 .6Hz), 8.65 (1H, dd, J=1.4Hz, 4.8Hz), 9.04 (1H, dd, J=1.6Hz, 8.0Hz), 9.50 (1H, s).

(4) 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-b]pyridine hydrochloride (Compound 65)
To a suspension of 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-b]pyridine (compound 65-3) (31.8 mg, 92.3 μmol) in methanol (3 mL), 4 M hydrochloric acid/dioxane solution (0.3 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (65) (23.6 mg).
^1H -NMR ( _CD3 OD) δ: 4.04 (3H, s), 7.04 (1H, d, J = 3.6Hz), 7.35-7.44 (2H, m), 7.64 (1H, d, J = 4.0Hz), 7.89-8.00 ( 1H, m), 8.40 (2H, dd, J=5.4Hz, 9.0Hz), 8.73-8.81 (1H, m), 9.66-9.76 (1H, m), 9.94-10.02 (1H, m).

Example 54
Synthesis of 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-c]pyridine hydrochloride (Compound 66)

(1) 4-(4-fluorophenyl)-7-methyl-N-(3-nitropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (Compound 66-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 19-1) (204 mg, 0.780 mmol) in N,N-dimethylformamide (5.0 mL), 4-amino-3-nitropyridine (130 mg, 0.936 mmol), cesium carbonate (381 mg, 1.17 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (74.4 mg, 156 μmol), and tris(dibenzylideneacetone)dipalladium (35.7 mg, 39.0 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography, and the title compound (66-1) (201 mg, 0.553 mmol, yield 71%) was obtained from the dichloromethane:methanol (50:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.90 (3H, s), 6.76 (1H, d, J = 3.6Hz), 7.18 (1H, d, J = 3.6Hz), 7.23-7.43 (2H, m), 8.13 -8.22 (2H, m), 8.59 (1H, d, J = 6.4Hz), 9.26 (1H, d, J = 6.4Hz), 9.39 (1H, s), 10.81 (1H, s).

(2) N ⁴ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyridine-3,4-diamine (Compound 66-2)
Palladium-activated carbon (Pd 10%) (40.3 mg, 37.9 μmol) was added to a solution of 4-(4-fluorophenyl)-7-methyl-N-(3-nitropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (compound 66-1) (202 mg, 0.553 mmol) in methanol (6 mL), and the mixture was stirred at room temperature under a hydrogen gas atmosphere for 16 hours. The reaction solution was filtered through Celite, and the resulting filtrate was evaporated under reduced pressure to give the title compound (66-2) (180 mg) as a crude product.
¹ H-NMR (CDCl ₃ ) δ: 3.74 (3H, s), 4.68 (2H, brs), 6.61 (1H, brs), 6.63 (1H, d, J = 3.6Hz), 6.79 (1H, dd, J = 5.0H z, 7.8Hz), 6.97 (1H, d, J=3.6Hz), 7.17-7.24 (2H, m), 7.93-7.99 (2H, m), 8.06-8.12 (2H, m).

(3) 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-c]pyridine (Compound 66-3)
To a solution of N ⁴ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyridine-3,4-diamine (compound 66-2) (180 mg, 0.539 mmol) in dioxane (5 mL), triethyl orthoformate (0.448 mL, 2.70 mmol) and p-toluenesulfonic acid monohydrate (30.8 mg, 0.162 mmol) were added, and the mixture was heated at 130°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (66-3) (79.2 mg, 0.230 mmol, two-step yield 43%) was obtained from the dichloromethane:methanol (40:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.01 (3H, s), 6.86 (1H, d, J=3.6Hz), 7.28-7.36 (3H, m), 8.22-8.30 (2H, m), 8.60-8.67 (2H, m), 9.21 (1H, s), 9.31 (1H, s).

(4) 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-c]pyridine hydrochloride (Compound 66)
To a suspension of 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1H-imidazo[4,5-c]pyridine (Compound 66-3) (79.2 mg, 0.230 mmol) in methanol (6 mL), 4 M hydrochloric acid/dioxane solution (0.6 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (66) (70.1 mg).
^1H -NMR ( _CD3 OD) δ: 4.04 (3H, s), 7.05 (1H, d, J = 4.0Hz), 7.39 (2H, dd, J = 8.4Hz, 9.2Hz), 7.65 (1H, d, J = 3.6Hz) ), 8.34-8.43 (2H, m), 8.77 (1H, d, J = 6.4Hz), 9.30 (1H, d, J = 6.4Hz), 9.46 (1H, s), 9.84 (1H, s).

Example 55
Synthesis of 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3H-imidazo[4,5-b]pyridine (Compound 67)

(1) 4-(4-fluorophenyl)-7-methyl-N-(3-nitropyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (Compound 67-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 19-1) (209 mg, 0.797 mmol) in N,N-dimethylformamide (5 mL), 2-amino-3-nitropyridine (133 mg, 0.957 mmol), cesium carbonate (391 mg, 1.20 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (75.8 mg, 159 μmol), and tris(dibenzylideneacetone)dipalladium (36.5 mg, 39.9 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (67-1) (203 mg, 0.557 mmol, yield 70%) was obtained from the dichloromethane:methanol (40:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.84 (3H, s), 6.73 (1H, d, J = 3.6Hz), 7.01-7.09 (1H, m), 7.13 (1H, d, J = 3.6Hz), 7.19-7.28 (2H, m), 8.13-8.21 (2H, m), 8.50 (1H, dd, J = 1.8Hz, 8.2Hz), 8.63 (1H, dd, J = 1.8Hz, 4.6Hz), 9.90 (1H, s).

(2) N ² -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyridine-2,3-diamine (Compound 67-2)
Palladium-activated carbon (Pd 10%) (40.6 mg, 38.2 μmol) was added to a mixed solution of 4-(4-fluorophenyl)-7-methyl-N-(3-nitropyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (compound 67-1) (203 mg, 0.557 mmol) in methanol (5 mL) and dichloromethane (2 mL), and the mixture was stirred at room temperature under a hydrogen gas atmosphere for 16 hours. The reaction solution was filtered through Celite, and the resulting filtrate was evaporated under reduced pressure to give the title compound (67-2) (88.8 mg) as a crude product.
^1H -NMR ( _CD3 OD) δ: 3.95 (3H, s), 6.93 (1H, d, J = 3.6Hz), 7.20 (1H, dd, J = 6.0Hz, 8.0Hz), 7.35-7 .42 (2H, m), 7.48-7.52 (2H, m), 7.78 (1H, dd, J=1.2Hz, 6.0Hz), 8.23-8.29 (2H, m).

(3) 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3H-imidazo[4,5-b]pyridine (Compound 67)
To a solution of N ² -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyridine-2,3-diamine (compound 67-2) (88.8 mg, 0.266 mmol) in dioxane (3 mL), triethyl orthoformate (0.221 mL, 1.33 mmol) and p-toluenesulfonic acid monohydrate (15.2 mg, 79.8 μmol) were added, and the mixture was heated at 130°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (67) (64.3 mg, 0.187 mmol, two-step yield 70%) was obtained from the dichloromethane fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.02 (3H, s), 6.89 (1H, d, J = 4.0Hz), 7.28-7.32 (3H, m), 7.33-7.39 (1H, m), 8.17 (1H , dd, J=1.2Hz, 8.0Hz), 8.30-8.38 (2H, m), 8.62 (1H, dd, J=1.4Hz, 4.6Hz), 9.18 (1H, s).

Example 56
Synthesis of 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3H-imidazo[4,5-c]pyridine hydrochloride (Compound 68)

(1) 4-(4-fluorophenyl)-7-methyl-N-(4-nitropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (Compound 68-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 19-1) (214 mg, 0.819 mmol) in N,N-dimethylformamide (5 mL), 3-amino-4-nitropyridine (137 mg, 0.983 mmol), cesium carbonate (401 mg, 1.23 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (78.2 mg, 164 μmol), and tris(dibenzylideneacetone)dipalladium (37.5 mg, 41.0 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (68-1) (271 mg, 0.744 mmol, yield 91%) was obtained from the dichloromethane:methanol (40:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.87 (3H, s), 6.74 (1H, d, J = 4.0Hz), 7.13 (1H, d, J = 3.6Hz), 7.21-7.30 (2H, m), 8.01 ( 1H, d, J = 5.6Hz), 8.14-8.22 (2H, m), 8.32 (1H, d, J = 5.6Hz), 10.19 (1H, s), 10.66 (1H, s).

(2) N ³ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyridine-3,4-diamine (Compound 68-2)
Palladium-activated carbon (Pd 10%) (5.6 mg, 5.26 μmol) was added to a mixed solution of 4-(4-fluorophenyl)-7-methyl-N-(4-nitropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (compound 68-1) (27.9 mg, 76.6 μmol) in methanol (2 mL) and dichloromethane (2 mL), and the mixture was stirred at room temperature under a hydrogen gas atmosphere for 16 hours. The reaction solution was filtered through Celite, and the resulting filtrate was evaporated under reduced pressure to give the title compound (68-2) (23.2 mg) as a crude product.

(3) 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3H-imidazo[4,5-c]pyridine (Compound 68-3)
To a solution of N ³ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyridine-3,4-diamine (Compound 68-2) (213 mg, 0.636 mmol) in dioxane (5 mL), triethyl orthoformate (0.529 mL, 3.18 mmol) and p-toluenesulfonic acid monohydrate (36.3 mg, 0.191 mmol) were added, and the mixture was heated at 130°C for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by preparative TLC (preparative thin layer chromatography) (amino silica gel), and the title compound (68-3) (29.4 mg, 85.4 μmol, two-step yield 13%) was obtained from the dichloromethane fraction.
¹ H-NMR (CDCl ₃ ) δ: 4.01 (3H, s), 6.87 (1H, d, J = 4.0Hz), 7.24-7.35 (3H, m), 7.78-7.84 (1H , m), 8.24-8.31 (2H, m), 8.59 (1H, d, J=5.2Hz), 9.38 (1H, s), 10.14 (1H, s).

(4) 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3H-imidazo[4,5-c]pyridine hydrochloride (Compound 68)
To a suspension of 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3H-imidazo[4,5-c]pyridine (compound 68-3) (28.2 mg, 81.9 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.2 mL) was added, and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (68) (22.0 mg).
^1H -NMR ( _CD3 OD) δ: 4.06 (3H, s), 7.05 (1H, d, J = 4.0Hz), 7.36-7.45 (2H, m), 7.66 (1H, d, J = 3.6Hz), 8.34-8.46 (3H, m), 8.71-8.77 (1H, m), 10.05 (1H, s), 10.27 (1H, s).

Example 57
Synthesis of 4-(4-fluorophenyl)-7-methyl-2-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 69)

(1) 4-(4-fluorophenyl)-7-methyl-2-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 69-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 19-1) (157 mg, 0.598 mmol) in N,N-dimethylformamide (5 mL), 4,5,6,7-tetrahydro-1H-benzo[d]imidazole (87.7 mg, 0.718 mmol), cesium carbonate (292 mg, 0.897 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (57.2 mg, 120 μmol), and tris(dibenzylideneacetone)dipalladium (27.4 mg, 29.9 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography (amino silica gel), and the title compound (69-1) (152 mg, 0.438 mmol, yield 73%) was obtained from the ethyl acetate:n-hexane (2:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 1.82-1.95 (4H, m), 2.66-2.74 (2H, m), 3.19-3.26 (2H, m), 3.89 (3H, s), 6.79 (1H, d , J=4.0Hz), 7.21 (1H, d, J=3.2Hz), 7.22-7.30 (2H, m), 8.16-8.24 (2H, m), 8.62 (1H, s).

(2) 4-(4-fluorophenyl)-7-methyl-2-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 69)
To a suspension of 4-(4-fluorophenyl)-7-methyl-2-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (Compound 69-1) (152 mg, 0.438 mmol) in methanol (6 mL), 4 M hydrochloric acid/dioxane solution (0.6 mL) was added and the mixture was stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to give the title compound (69) (133 mg).
^1H -NMR ( _CD3 OD) δ: 1.95-2.06 (4H, m), 2.76-2.83 (2H, m), 3.35-3.42 (2H, m), 3.96 (3H, s), 7.06 (1H, d, J=3.6Hz), 7.32-7.41 (2H, m), 7.67 (1H, d, J=3.6Hz), 8.32-8.40 (2H, m), 9.79 (1H, s).

Compound (72) was synthesized from compound (19-1) according to the synthesis method of compound (69).
2-(5,6-Dihydrocyclopenta[d]imidazol-1(4H)-yl)-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride (Compound 72)
^1H -NMR ( _CD3 OD) δ: 2.73-2.83 (2H, m), 2.92-2.99 (2H, m), 3.41-3.49 (2H, m), 3.95 (3H, s), 7.03-7.09 ( 1H, m), 7.32-7.41 (2H, m), 7.66 (1H, dd, J=1.4Hz, 3.8Hz), 8.32-8.41 (2H, m), 9.72 (1H, s).

Example 58
Synthesis of 9-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-9H-purine (Compound 70)

(1) N ⁴ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyrimidine-4,5-diamine (Compound 70-1)
(2) N ⁵ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyrimidine-4,5-diamine (Compound 71-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (Compound 19-1) (166 mg, 0.632 mmol) in N,N-dimethylformamide (5 mL), 4,5-diaminopyrimidine (83.5 mg, 0.758 mmol), cesium carbonate (309 mg, 0.948 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (60.1 mg, 126 μmol), and tris(dibenzylideneacetone)dipalladium (28.9 mg, 31.6 μmol) were added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesizer. After cooling, water was added to the reaction solution, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography (amino silica gel), and from the dichloromethane:ethyl acetate (1:2) fraction, the title compound (70-1) (21.4 mg, 63.8 μmol, yield 10%) and the title compound (71-1) (46.4 mg, 0.138 mmol, yield 22%) were obtained.
(Compound 70-1)
¹ H-NMR (CDCl ₃ ) δ: 3.79 (3H, s), 4.73 (2H, brs), 6.68 (1H, d, J = 3.6Hz), 7.06 (1H, d, J = 4.0Hz), 7. 19-7.30 (2H, m), 7.66-7.73 (1H, m), 8.04-8.12 (2H, m), 8.19 (1H, s), 8.48 (1H, s).
(Compound 71-1)
¹ H-NMR (CDCl ₃ ) δ: 3.73 (3H, s), 5.30 (2H, brs), 6.45 (1H, brs), 6.64 (1H, d, J = 3.6Hz), 6.99 (1H, d, J = 3.6Hz), 7.21 (2H, dd, J=8.8Hz, 8.8Hz), 8.04-8.12 (2H, m), 8.50 (1H, s), 8.56 (1H, s).

(3) 9-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-9H-purine (Compound 70)
To a solution of N ⁴ -(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)pyrimidine-4,5-diamine (compound 70-1) (21.4 mg, 63.8 μmol) in dioxane (1 mL), triethyl orthoformate (53.0 μL, 0.319 mmol) and p-toluenesulfonic acid monohydrate (3.6 mg, 0.191 mmol) were added, and the mixture was heated at 130° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (amino silica gel), and the title compound (70) (14.2 mg, 41.1 μmol, yield 65%) was obtained from the dichloromethane:ethyl acetate (1:1) fraction.
¹ H-NMR (CDCl ₃ ) δ: 3.99 (3H, s), 6.88 (1H, d, J=3.6Hz), 7.23-7.34 (3H, m), 8.26-8.34 (2H, m), 9.19 (2H, s), 9.24 (1H, s).

Compound (71) was synthesized from compound (71-1) in accordance with the synthesis method for compound (70) from compound (70-1).
7-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-7H-purine (Compound 71)
¹ H-NMR (CDCl ₃ ) δ: 3.99 (3H, s), 6.87 (1H, d, J=3.6Hz), 7.24-7.37 (3H, m), 8.19-8.29 (2H, m), 9.20-9.30 (1H, m), 9.55 (1H, s), 10.10 (1H, s).

Example 59
Synthesis of 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine hydrochloride (Compound 76)

(1) tert-Butyl 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate (Compound 76-1)
(2) tert-butyl 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate (Compound 77-1)
To a solution of 2-chloro-4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (compound 19-1) (246 mg, 0.939 mmol) in N,N-dimethylformamide (6 mL), tert-butyl 1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate (252 mg, 1.13 mmol), cesium carbonate (459 mg, 1.41 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (89.6 mg, 188 μmol), and tris(dibenzylideneacetone)dipalladium (43.0 mg, 47.0 μmol) were added, and the mixture was heated at 160 ° C. for 10 minutes using a microwave synthesizer. After cooling, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography, and from the dichloromethane:acetone (10:1) fraction, the title compound (76-1) (99.0 mg, 0.221 mmol, yield 24%) and compound (77-1) (85.7 mg, 0.191 mmol, yield 20%) were obtained.
(Compound 76-1)
¹ H-NMR (CDCl ₃ ) δ: 1.51 (9H, s), 2.70-2.88 (2H, m), 3.70-3.85 (2H, m), 3.91 (3H, s), 5.13 (2H, s), 6.80 (1H, d, J=3.2Hz), 7.18-7.32 (3H, m), 8.15-8.24 (2H, m), 8.72 (1H, s).
(Compound 77-1)
¹ H-NMR (CDCl ₃ ) δ: 1.51 (9H, s), 3.30-3.41 (2H, m), 3.75-3.85 (2H, m), 3.90 (3H, s), 4.57 (2H, s), 6.81 (1H, d, J=3.6Hz), 7.20-7.32 (3H, m), 8.15-8.24 (2H, m), 8.68 (1H, s).

(3) 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine hydrochloride (Compound 76)
To a suspension of tert-butyl 3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-3,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate (Compound 76-1) (89.6 mg, 0.200 mmol) in ethanol (2 mL), a 4 M hydrochloric acid/dioxane solution (1 mL) was added, and the mixture was heated and stirred at 75° C. for 30 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (76) (65.7 mg).
^1H -NMR (DMSO- _d6 ) δ: 2.93-3.07 (2H, m), 3.43-3.54 (2H, m), 3.91 (3H, s), 4.87 (2H, s), 7.04-7.12 (1H, m), 7.47 (2H, dd, J=8.0Hz, 8.8Hz), 7.80-7.87 (1H, m), 8.33-8.44 (2H, m), 9.60-9.72 (1H, m).

Example 60
Synthesis of 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine hydrochloride (Compound 77)

(1) 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine hydrochloride (Compound 77-2)
To a suspension of tert-butyl 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate (Compound 77-1) (76.2 mg, 0.170 mmol) in ethanol (2 mL), 4 M hydrochloric acid/dioxane solution (1 mL) was added, and the mixture was stirred at 75° C. for 30 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (77-2) (56.3 mg).
^1H -NMR (DMSO- _d6 ) δ: 3.42-3.78 (4H, m), 3.90 (3H, s), 4.26 (2H, s), 7.06 (1H, d, J = 3.6Hz), 7.47 (2H, dd, J = 8.8 Hz, 8.8Hz), 7.80 (1H, d, J=7.2Hz), 8.33-8.43 (2H, m), 8.94-9.09 (1H, m), 9.42-9.64 (1H, m).

(2) 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine (Compound 77-3)
To a suspension of 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine hydrochloride (compound 77-2) (20.4 mg, 53.0 μmol) in methanol (1 mL), sodium triacetoxyborohydride (44.9 mg, 0.212 mmol), 37% aqueous formaldehyde solution (26 μL, 0.265 mmol), and acetic acid (4 μL, 63.6 μmol) were added, and the mixture was stirred at room temperature for 13 hours. Water was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under reduced pressure to obtain the title compound (77-3) (18.3 mg, 50.5 μmol).
¹ H-NMR (CDCl ₃ ) δ: 2.54 (3H, s), 2.81 (2H, t, J = 6.0Hz), 3.37 (2H, t, J = 5.8Hz), 3.58 (2H, s), 3.87 ( 3H, s), 6.77 (1H, d, J=3.6Hz), 7.16-7.30 (3H, m), 8.12-8.22 (2H, m), 8.64 (1H, s).

(3) 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine hydrochloride (Compound 77)
To a suspension of 1-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine (compound 77-3) (18.3 mg, 50.5 μmol) in methanol (2 mL), 4 M hydrochloric acid/dioxane solution (0.2 mL) was added and stirred at room temperature for 10 minutes. The solvent was evaporated under reduced pressure, and then ethyl acetate and n-hexane were added to the residue. The resulting solid was collected by filtration and dried to obtain the title compound (77) (10.3 mg).
^1H -NMR ( _CD3 OD) δ: 3.19 (3H, s), 3.27-3.34 (6H, m), 3.97 (3H, s), 7.06 (1H, d, J = 3.6Hz), 7.37 (2 H, dd, J=8.8Hz, 8.8Hz), 7.64-7.70 (1H, m), 8.31-8.39 (2H, m), 9.71-9.77 (1H, m).

Compound (78) was synthesized from compound (76) in accordance with the synthesis method for compound (77) from compound (77-2).
3-(4-(4-fluorophenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine hydrochloride (Compound 78)
^1H -NMR ( _CD3 OD) δ: 3.23 (3H, s), 3.25-3.34 (6H, m), 4.00 (3H, s), 7.08 (1H, d, J = 3.6Hz), 7.3 5-7.43 (2H, m), 7.70 (1H, d, J=3.6Hz), 8.32-8.40 (2H, m), 9.94-10.06 (1H, m).

Test Example 1 (in vitro antitumor activity test)
(1) Antitumor Activity against Breast Cancer-Derived Cell Line MDA-MB-468 The antitumor activity of Compounds 1 to 100 was evaluated by XTT assay (Table 1). The XTT assay method is as follows. MDA-MB-468 (ATCC number: HTB-132) was purchased from the American Type Culture Collection (ATCC). MDA-MB-468 was cultured in DMEM medium (Thermo Fisher Scientific) supplemented with 10% fetal bovine serum (Thermo Fisher Scientific) and 0.1 mg/mL kanamycin sulfate (Thermo Fisher Scientific) at 37°C under 5% _CO2 conditions.
Day 1: MDA-MB-468 cells were treated with trypsin/EDTA (Thermo Fisher Scientific) to form single floating cells, and a single-cell suspension of 4 x ¹⁰ cells per mL was prepared in DMEM medium (supplemented with 10% fetal bovine serum and 0.1 mg/mL kanamycin sulfate). The cells were then seeded into a 96-well plate (Thermo Fisher Scientific) at 4 x ¹⁰ cells/well.
Day 2: The sample was dissolved in DMSO (Fujifilm Wako Pure Chemical Industries, Ltd.) and then diluted in RPMI 1640 medium (containing 10% fetal bovine serum and 0.1 mg/mL kanamycin sulfate) to prepare a dilution series ranging from 0.000076 μM to 5 μM. 100 μL of each solution was added to the wells seeded with cells on Day 1, and the cells were cultured at 37°C in ₅ % CO for 72 hours.

To use this as a reference point (time zero) when calculating the 50% growth inhibitory concentration (GI ₅₀ value), 100 μL of RPMI 1640 medium (supplemented with 10% fetal bovine serum and 0.1 mg/mL kanamycin sulfate) and 50 μL of XTT solution (1 mg/mL XTT (Polysciences), 2.5 mM phenazine methosulfate (Merck)/phenol red-free RPMI 1640 (Thermo Fisher Scientific)) were added to a plate on Day 1 on which cells had been seeded in the same manner as for adding the sample. After incubation for 4 hours, the absorbance at 450 nm was measured using a plate reader MTP-300 (CORONA ELECTRIC) and defined as A ₄₅₀ (TZ).
Day 5: 50 μL of XTT solution was added to each plate, and after incubation for 4 hours, the absorbance at 450 nm was measured using an MTP-300 to obtain A ₄₅₀ (Day 5).
The GI ₅₀ value of each sample was calculated by taking A ₄₅₀ (TZ) as a proliferation rate of 0% and A ₄₅₀ (Day 5) of a well to which no sample was added (control) as a proliferation rate of 100%. The calculation formula is shown in FIG.

The concentration at the measurement point where the proliferation rate is higher than 50% on either side of the 50% proliferation rate is A μM, the proliferation rate at A μM is C%, the concentration at the measurement point where the proliferation rate is lower than 50% on either side of the 50% proliferation rate is B μM, and the proliferation rate at B μM is D%.
C = (A ₄₅₀ (Day 5) - _{A 450} (TZ) when treated at a concentration of A μM) / (A ₄₅₀ (Day 5) - A ₄₅₀ (TZ) of the control) × 100
D = (A ₄₅₀ (Day 5) - A ₄₅₀ (TZ) when treated with a concentration of B μM) / (A ₄₅₀ (Day 5) - A ₄₅₀ (TZ) of the control) × 100

a=(CD)/LOG(A/B)
b=C-(LOG(A)-6)a
GI ₅₀ = 10^((50-b+6a)/a)

Table 1 shows the GI ₅₀ values (μM) of Compounds 1 to 100 against the breast cancer-derived cell line MDA-MB-468.

(2) Antitumor activity against various tumor cell lines Compound 32 was subjected to XTT tests against multiple cell lines, and GI ₅₀ values were determined using the same method as in Figure 1. Each cell was cultured under optimal conditions, and the number of cells seeded was optimized for each cell type. The single-cell suspension concentration (cell suspension concentration) is shown in Table 2. As shown in Table 2, compound 32 exhibited strong antitumor activity against cell lines derived from a wide range of cancer types.

Test Example 2 (in vivo antitumor activity test)
The in vivo antitumor activity of compound 32 was evaluated using tumor-bearing model mice transplanted with breast cancer-derived cell line MDA-MB-468.
NOD-scid mice (NOD.CB17-Prkdc ^scid /J, 6-week-old female), which are severely immunodeficient mice, were purchased from Jackson Laboratory Japan. A suspension of MDA-MB-468 cells (2 x ¹⁰ cells/mouse) was subcutaneously transplanted into the NOD-scid mice, and when the tumor size reached 100 mm ³ to 300 mm ^{3 ,} the mice were divided into groups (5 mice per group) and the administration of the test sample was initiated.
Compound 32 was dissolved in a 5% glucose solution and administered via the tail vein at 1.0, 2.5, or 5.0 mg/kg three times every four days (Day 0, Day 4, and Day 8), and tumor diameter and body weight were measured over time until Day 29. The tumor size (major diameter × minor diameter × minor diameter × 1/2) on the day administration began (Day 0) was set as 1, and the relative tumor growth rate was calculated.
As a result, tumor growth was suppressed in all treatment groups. In particular, the 2.5 and 5 mg/kg Compound 32 treatment groups showed a relative tumor growth rate of 1 or less during the observation period, and the relative tumor growth rates on Day 29 were 0.75 and 0.35, respectively, demonstrating that the tumor shrinkage effect was maintained (Figure 2). The percentage of the relative tumor growth rate of the control group to the relative tumor growth rate of the Compound 32 treatment group on Day 29 was defined as T/C (%). The relative tumor growth rate of the control group on Day 29 was 8.55, and the T/C of the 2.5 and 5.0 mg/kg Compound 32 treatment groups was 8.8% and 4.1%, respectively.
The weight change of the mice was shown with the weight on Day 0 as the reference weight (0) (FIG. 3). No significant weight loss was observed due to the administration of the test substance.

Claims (8)

The following general formula (1)
(In the formula, the Ar ring group represents a monocyclic or bicondensed ring aromatic heterocyclic group or an aromatic hydrocarbon group having 6 to 10 carbon atoms;
Het ring represents a pyrrole ring, a pyrrolidine ring, a thiophene ring, a furan ring, a pyrazole ring, or a pyridine ring;
A, B, C, and D are the same or different and represent C, CH, or N, and the number of N among A, B, C, and D is up to two, and the dashed line in this ring indicates that a double bond may be present (here, when the dashed line represents a double bond and A, B, C, or D is N, R ¹ , R ² , R ³ , and R ⁴ do not exist on the N);
R ¹ , R ² , R ³ and R ⁴ are the same or different and each represent a hydrogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a hydroxy group, a hydroxyalkyl group, an alkanoyl group or an alkoxycarbonyl group;
^R5 and ^R6 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, a halogenoalkyl group, a hydroxyalkyl group, an alkanoyl group, a benzoyl group, an oxo group, or a carbamoyl group optionally substituted with one or two alkyl groups;
^R7 and ^R8 are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkoxyalkyl group, a hydroxy group, or an amino group optionally substituted with one or two alkyl groups;
n represents the number 0 or 1)
A pyrimidine-containing fused ring compound represented by the following formula: The pyrimidine-containing fused ring compound, its salt, or solvate thereof according to claim 1, wherein the Ar ring group is a pyrrolopyrimidyl group, a pyrrolopyridyl group, a dihydropyrrolopyridyl group, a tetrahydropyridopyridyl group, a tetrahydroquinolyl group, a tetrahydroisoquinolyl group, an ethylenedioxyphenyl group, an ethylenedioxypyridyl group, an indolyl group, an isoindolyl group, an indolinyl group, an isoindolinyl group, a pyridyl group, a pyrimidyl group, an imidazolyl group, a pyrazolyl group, a pyrrolyl group, a thienyl group, a furyl group, an indenyl group, a naphthyl group, or a phenyl group. The pyrimidine-containing fused ring compound, its salt, or solvate thereof according to claim 1 or 2, wherein the ring containing A, B, C, and D is a benzene ring, cyclohexane ring, cyclopentane ring, pyridine ring, pyrimidine ring, or piperidine ring. A pharmaceutical composition comprising the pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to any one of claims 1 to 3, and a pharmaceutically acceptable carrier. A malignant tumor therapeutic agent containing as an active ingredient the pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to any one of claims 1 to 3. A pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to any one of claims 1 to 3 for use in the treatment of malignant tumors. Use of the pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to any one of claims 1 to 3 for the manufacture of a therapeutic agent for malignant tumors. A method for treating malignant tumors, comprising administering the pyrimidine-containing fused ring compound, its salt, or a solvate thereof according to any one of claims 1 to 3.