CN112661668B - N-substituted amide compound and preparation method thereof - Google Patents
N-substituted amide compound and preparation method thereof Download PDFInfo
- Publication number
- CN112661668B CN112661668B CN202011622775.4A CN202011622775A CN112661668B CN 112661668 B CN112661668 B CN 112661668B CN 202011622775 A CN202011622775 A CN 202011622775A CN 112661668 B CN112661668 B CN 112661668B
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- sodium
- alkyl
- substituted amide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the field of intermediate synthesis, and discloses a method for synthesizingN-substituted amide compound and preparation method thereof, wherein the compound has a structure shown in formula (I), and R in formula (I) 1 Selected from C 1‑6 At least one of alkyl, phenyl substituted with a substituent X selected from C 1‑6 Alkyl, C 1‑6 At least one of alkoxy and halogen, R 2 、R 3 、R 4 、R 5 、R 6 Each independently selected from C 1‑6 Alkyl, C 1‑6 When the N-substituted amide compound provided by the invention is used for preparing a compound shown in a formula (III), the N-substituted amide compound has the advantages of low raw material cost, mild reaction, high yield and high hydrolysis safety.
Description
Technical Field
The invention relates to an N-substituted amide compound and a method for preparing the N-substituted amide compound shown in a formula (I).
Background
At present, a common method for synthesizing 2- (4-chlorophenoxy) -propoxyamine is to protect by using ketoxime, ketoxime derivative, N-hydroxyphthalimide and derivatives thereof and other groups, and then deprotect the mixture to obtain the product. The method has detailed synthetic reports in journals such as Tetrahedron Letters,1988, vol.29,701-704 and J.org.chem.2005,70, 6303-6312; the above-described method of synthesizing 2- (4-chlorophenoxy) -propoxyamine is also used to synthesize such intermediates in the patents CN1055459C, TW232646B, etc. by basf. The method has the following defects: the whole synthesis process has the disadvantages of expensive reaction raw materials, low reaction yield, and poor reaction safety, and the deprotection process must be applied to compounds such as hydrazine and the like.
Disclosure of Invention
The invention aims to solve the problems of low yield and poor reaction safety in the preparation of 2- (4-chlorophenoxy) -propoxyamine in the prior art.
In order to achieve the above object, a first aspect of the present invention provides an N-substituted amide-based compound having a structure represented by formula (I),
in formula (I), R 1 Selected from C 1-6 At least one of alkyl, phenyl substituted with a substituent X selected from C 1-6 Alkyl, C 1-6 At least one of alkoxy and halogen, R 2 、R 3 、R 4 、R 5 、R 6 Each independently selected from C 1-6 Alkyl, C 1-6 At least one of alkoxy, halogen and H.
In a second aspect, the present invention provides a process for preparing an N-substituted amide compound represented by the formula (I), which comprises: contacting a compound shown in a formula (II-1) with a compound shown in a formula (II-2);
wherein R is 1 、R 2 、R 3 、R 4 、R 5 、R 6 Is the same as the definition set forth above;
R 7 selected from C 1-6 Alkyl, phenyl, substituted X 1 At least one of substituted phenyl groups, said X 1 Selected from C 1-6 Alkyl, C 1-6 At least one of alkoxy and halogen.
The third aspect of the present invention provides the use of the N-substituted amide compound represented by the formula (I) described above for the preparation of the compound represented by the formula (III),
when the N-substituted amide compound provided by the invention is used for preparing the 2- (4-chlorophenoxy) -propoxyamine shown in the formula (III), the N-substituted amide compound has the advantages of low raw material cost, mild reaction, high yield and high hydrolysis safety, and is suitable for industrial production.
Detailed Description
The endpoints and any values of the ranges disclosed herein are not limited to the precise range or value, and are understood to encompass values approaching those ranges or values. For numerical ranges, one or more new numerical ranges may be found between the endpoints of each range, between the endpoint of each range and the individual point value, and between the individual point value, in combination with each other, and are to be considered as specifically disclosed herein.
In the present invention, "C 1-6 The alkyl group "of (a) represents an alkyl group having a total of 1 to 6 carbon atoms, including a straight-chain alkyl group, a branched-chain alkyl group or a cycloalkyl group, and may be, for example, a straight-chain alkyl group, a branched-chain alkyl group or a cycloalkyl group having a total of 1, 2, 3, 4, 5, 6 carbon atoms, and may be, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, methylcyclopropyl, ethylcyclopropyl, cyclopentyl, methylcyclopentyl, cyclohexyl and the like. For "C 1-4 The "alkyl group" of (a) has a similar explanation to this except that the number of carbon atoms is different.
“C 1-6 Alkoxy "of (a) denotes an alkoxy group having a total number of carbon atoms of 1 to 6, including straight-chain alkoxy, branched alkoxy or epoxyalkyl groups, and may be, for example, straight-chain alkoxy, branched alkoxy or cycloalkyl having a total number of carbon atoms of 1, 2, 3, 4, 5, 6, and may be, for example, methoxy, ethoxy, n-propyl, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, isopentyloxyEtc. For "C 1-6 The "alkoxy group" of (a) has a similar explanation to this except that the number of carbon atoms is different.
In the present invention, unless otherwise specified, the N-substituted amide compound is a racemate.
As described above, the first aspect of the present invention provides an N-substituted amide compound having a structure represented by formula (I),
in formula (I), R 1 Selected from C 1-6 At least one of alkyl, phenyl substituted with a substituent X selected from C 1-6 Alkyl, C 1-6 At least one of alkoxy and halogen, R 2 、R 3 、R 4 、R 5 、R 6 Each independently selected from C 1-6 Alkyl, C 1-6 At least one of alkoxy, halogen and H.
Preferably, in formula (I), R 1 Selected from C 1-4 At least one of alkyl, phenyl substituted with a substituent X selected from C 1-4 Alkyl, C 1-4 At least one of alkoxy, F, cl, br, I, R 2 、R 3 、R 4 、R 5 、R 6 Each independently selected from C 1-4 Alkyl, C 1-6 At least one of an alkoxy group and F, cl, br, I, H.
More preferably, in formula (I), R 1 At least one selected from methyl, ethyl, propyl, n-butyl, tert-butyl, methoxy, ethoxy and phenyl, R 2 、R 3 、R 4 、R 5 、R 6 Each independently selected from at least one of F, cl, br, I, H, methyl and ethyl.
Particularly preferred, the N-substituted amide compound is selected from the following compounds:
a compound a1;
compound a2:
compound a3:
compound a4;
compound a5:
compound a6:
compound a7:
compound a8:
compound a9:
compound a10:
compound a11:
compound a12:
the present invention is not particularly limited in the preparation method for preparing the compound of the general structure represented by the formula (I), and a person skilled in the art can determine a suitable synthesis method according to the preparation method of the structural formula of the compound provided by the present invention in combination with the preparation example.
Further, the preparation methods of some compounds are given in the preparation examples of the present invention by way of example, and those skilled in the art can obtain the compounds provided in the present invention according to the preparation methods of these exemplary preparation examples. The present invention is not described in detail herein with respect to specific methods for preparing the various compounds of the present invention, and those skilled in the art should not be construed as limiting the invention.
However, in order to obtain the N-substituted amide compound represented by the formula (I) in a higher yield and with a higher purity, the present invention provides a preferred embodiment for producing the N-substituted amide compound represented by the formula (I). As described above, the second aspect of the present invention provides a process for producing an N-substituted amide compound represented by the formula (I), which comprises: contacting a compound shown in a formula (II-1) with a compound shown in a formula (II-2);
wherein R is 1 、R 2 、R 3 、R 4 、R 5 、R 6 Is the same as the definition set forth above;
R 7 selected from C 1-6 Alkyl, phenyl, substituted X 1 At least one of substituted phenyl groups, said X 1 Selected from C 1-6 Alkyl, C 1-6 At least one of alkoxy and halogen.
Preferably, said R 7 At least one selected from methyl, ethyl, n-propyl, n-butyl, tert-butyl, methoxy, ethoxy and phenyl.
Preferably, the contact reaction is carried out in the presence of solvent I and acid-binding agent I.
Preferably, the acid binding agent I is at least one selected from potassium carbonate, sodium methoxide, sodium hydroxide, potassium hydroxide, sodium hydride, sodium tert-butoxide and sodium isopropoxide.
Preferably, the solvent I is at least one selected from benzene, toluene, xylene, methylene dichloride, dichloroethane, N-dimethylformamide, N-hydroxypyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, tetrahydrofuran and acetonitrile.
Preferably, the conditions of the contact reaction at least satisfy: the temperature is 20-150 ℃.
Preferably, the compound shown in the formula (II-1), the compound shown in the formula (II-2) and the acid binding agent I are used in a molar ratio of 1: (1-10): (1-10).
The amount of the solvent used in the present invention is not particularly limited, and the amount of the solvent is exemplified hereinafter, and those skilled in the art should not understand the limitation of the present invention.
The substituents in the N-substituted amide compounds of the structure shown in the formula (I) in the second aspect of the present invention and the following description are the same as the substituents in the N-substituted amide compounds in the first aspect of the present invention, and in order to avoid repetition, specific types of the N-substituted amide compounds are not described herein in detail, and those skilled in the art should not understand that the present invention is limited thereto.
The preparation method of the present invention may further include a necessary post-treatment step to remove, for example, impurities or unreacted raw materials, and the present invention is not particularly limited to the specific operation of the post-treatment step, and the post-treatment may be performed by those skilled in the art using various operations (e.g., extraction, washing, drying, etc.) which are conventional in the art, and the present invention will not be described in detail herein, and the present invention should not be construed as being limited thereto.
The method of the present invention is not particularly limited as to the source of the compound represented by the formula (II-1) and the compound represented by the formula (II-2), and may be designed and synthesized by, for example, commercially available methods, or by selecting synthetic methods known in the art depending on substituents.
As described above, the third aspect of the present invention provides the use of the N-substituted amide compound represented by the above formula (I) for preparing the compound represented by the formula (III),
the invention will be described in detail below by way of examples. The reagents in the examples below were all commercially available analytically pure products without specific explanation.
Unless otherwise specified, the room temperature or the normal temperature is 25.+ -. 1 ℃ in the examples below.
In the examples below, the content of the product was determined by liquid chromatography.
2- (4-chloro-phenoxy) -propanol, the preparation method is as follows:
parachlorophenol (0.515 mol), potassium carbonate (0.5 mol) and petroleum ether (500 ml) are added into a reaction bottle for reflux water separation, methyl chloropropionate (0.5 mol) is dropwise added after reaction for 30min, reflux water separation is continued for 12h under the condition of 65 ℃ after the dropwise addition, water (100 ml) is added after HPLC (high performance liquid chromatography) detects that the methyl chloropropionate is basically unchanged, the mixture is stirred and then stands for layering, an organic phase is washed twice by water, petroleum ether is removed under reduced pressure, and 2- (4-chloro-phenoxy) -methyl propionate is obtained.
Sodium borohydride (1 mol), anhydrous calcium chloride (0.05 mol), toluene (500 ml) and ethanol (500 ml) are added into a reaction bottle, after being uniformly mixed, the prepared 2- (4-chloro-phenoxy) -methyl propionate (0.5 mol) is continuously added dropwise, after the dripping is finished, the reaction is carried out for 4 hours under the condition of 30 ℃, after the HPLC detection of the content of the 2-p-chlorophenoxy methyl propionate being less than 1wt%, 20wt% ammonium chloride aqueous solution (calculated as pure substances) is added for hydrolysis reaction, the hydrolysis temperature is 30 ℃ and the hydrolysis time is 1 hour, after the reaction is finished, the mixture is stood for layering, toluene is used for extracting twice, the organic phase is combined, and the 2- (4-chlorophenoxy) -1-propanol is obtained after the solvent is removed, the yield is 95%, and the chemical purity is 94%.
Methane sulfonyl chloride: the chemical purity is more than 98%, and the product is purchased from national medicine group chemical reagent limited company.
Preparation example 1: preparation of the Compound represented by formula (II-1-1)
Formula (II-1-1):
2- (4-chloro-phenoxy) -propanol (0.5 mol), triethylamine (0.85 mol) and toluene (500 ml) shown in formula (II-3) are added into a reaction bottle, methanesulfonyl chloride (0.6 mol) shown in formula (II-4) is added dropwise, after the dropwise addition is finished, the mixture is reacted for 3 hours at 30 ℃, after HPLC detection, the 2- (4-chloro-phenoxy) -propanol shown in formula (II-3) is less than 1wt%, water is added, stirring and layering are carried out, and the toluene is removed from an organic phase to obtain the compound shown in formula (II-1-1).
Preparation example 2: preparation of Compound a1
Compound a1:formula (II-2-1): />
Adding a compound (0.5 mol) shown in a formula (II-1-1), a compound (0.85 mol) shown in a formula (II-2-1) and DMSO (600 ml) into a reaction bottle, stirring and dissolving, adding sodium hydroxide (2 mol), reacting for 12 hours at 60 ℃, detecting that the compound shown in the formula (II-1-1) is basically unchanged by HPLC, distilling to remove DMSO, dissolving the residual organic phase in the bottle, extracting with dichloromethane three times, and removing dichloromethane to obtain the compound a1.
The characterization data for specific yields and substituent conditions are in part as follows:
compound a1 yield = moles of compound a 1/moles of 2- (4-chloro-phenoxy) -propanol, and the yields of other compounds were calculated similarly to compound a1.
The following compounds were obtained using a similar procedure (alternative starting materials) to that of preparation 1 and preparation 2 and characterized as follows:
a compound a1;the yield thereof was found to be 80.07%, 1 H NMR(400MHz,CDCl 3 )δ7.42–7.23(m,2H),6.99–6.79(m,2H),4.66–4.45(m,1H),4.61(s,1H),3.80(d,J＝5.6Hz,2H),2.02(s,3H),1.31(d,J＝6.4Hz,3H)。
compound a2:the yield thereof was found to be 78.13%, 1 H NMR(400MHz,CDCl 3 )δ7.34–7.29(m,2H),6.90–6.83(m,2H),4.62–4.55(m,1H),4.35(s,1H),3.80(d,J＝5.6Hz,2H),2.34(q,J＝7.6Hz,2H),1.31(d,J＝6.4Hz,3H),1.12(t,J＝8.0Hz,3H)。
compound a7:the yield thereof was found to be 75.01%, 1 H NMR(400MHz,CDCl 3 δ7.94–7.90(m,2H),7.61–7.54(m,1H),7.51–7.44(m,2H),7.32–7.27(m,2H),6.90–6.84(m,2H),4.74(s,1H),4.66–4.52(m,1H),3.86(d,J＝5.6Hz,2H),1.32(d,J＝6.4Hz,3H)。
compound a10:the yield thereof was found to be 73.12%, 1 H NMR(400MHz,CDCl 3 )δ7.80–7.76(m,2H),7.32–7.28(m,2H),7.28–7.24(m,2H),6.89–6.85(m,2H),4.97(s,1H),4.66–4.54(m,1H),3.86(d,J＝5.6Hz,2H),2.42(s,3H),1.32(d,J＝6.4Hz,3H)。
example 1: preparing a compound shown in a formula (III).
The compound (0.5 mol) shown in the formula (I) shown in Table 1 is taken as a raw material, added into a reaction bottle together with ethanol (1 mol), 30wt% hydrochloric acid (calculated by hydrogen ions, 1 mol) is added dropwise, the reaction is carried out for 2 hours under the condition of 30 ℃, after the content of the compound shown in the formula (I) is detected to be less than 1wt% by HPLC, ethanol in the system is removed, 30wt% sodium hydroxide solution is added to adjust the pH value to 14, dichloromethane is used for extraction twice, dichloromethane is removed, the compound shown in the formula (III) is obtained, the yield of the compound shown in the formula (III) is calculated, and the specific results are shown in Table 1.
Comparative example 1
Synthesizing a compound represented by formula (IV): (Compound B1)
The compound (0.5 mol) of the formula (II-1-1) obtained in the preparation example 1, N-hydroxyphthalimide (0.65 mol) and DMF (600 ml) are added into a reaction bottle, potassium carbonate (1 mol) is added after stirring and dissolution, the reaction is carried out for 12 hours at 80 ℃, after the HPLC detection of the compound of the formula (II-1-1) is basically unchanged, DMF is distilled off, the residual organic phase in the bottle is dissolved by water, the solution is extracted three times by using dichloromethane, and the dichloromethane is removed to obtain the compound of the formula (IV).
Synthesis of Compound represented by formula (III)
The compound shown in the formula (IV) obtained by the preparation is taken as a raw material (0.5 mol), hydrazine hydrate (1 mol) and methylene dichloride (600 ml) are added into a reaction bottle to react for 8 hours at the temperature of 60 ℃, after the content of the compound shown in the formula (IV) is detected to be less than 1 weight percent by HPLC, the suspension is filtered, methylene dichloride is removed to obtain the compound shown in the formula (III), and the yield of the compound shown in the formula (III) is calculated, and the specific result is shown in the table 1.
Yield of the compound represented by formula (III) in table 1 = moles of the compound represented by formula (III)/moles of the starting material in table 1;
the chemical purity of the compound represented by formula (III) in table 1 is the content of the compound represented by formula (III) in terms of pure substance in the obtained product.
TABLE 1
As can be seen from the results of Table 1, the yield of the compound represented by formula (III) obtained from the compound of the present invention was high.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, a number of simple variants of the technical solution of the invention are possible, including combinations of the individual technical features in any other suitable way, which simple variants and combinations should likewise be regarded as being disclosed by the invention, all falling within the scope of protection of the invention.
Claims (5)
1. A process for preparing an N-substituted amide compound of formula (I), comprising: contacting a compound shown in a formula (II-1) with a compound shown in a formula (II-2);
wherein R in the formula (I), the formula (II-1) and the formula (II-2) 1 At least one selected from methyl, ethyl, propyl, n-butyl, tert-butyl, methoxy, ethoxy and phenyl, R 2 、R 3 、R 4 、R 5 、R 6 Each independently selected from at least one of F, cl, br, I, H, methyl, ethyl;
R 7 selected from C 1-6 Alkyl, phenyl, substituted X 1 At least one of substituted phenyl groups, said X 1 Selected from C 1-6 Alkyl, C 1-6 At least one of an alkoxy group and a halogen;
the contact reaction is carried out in the presence of a solvent I and an acid binding agent I;
the solvent I is at least one selected from benzene, toluene, xylene, dichloromethane, dichloroethane, N-dimethylformamide, N-hydroxypyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, tetrahydrofuran and acetonitrile;
the acid binding agent I is at least one selected from potassium carbonate, sodium methoxide, sodium hydroxide, potassium hydroxide, sodium hydride, sodium tert-butoxide and sodium isopropoxide.
2. The method according to claim 1, wherein the acid binding agent I is selected from at least one of potassium carbonate, sodium hydroxide, sodium hydride, sodium tert-butoxide.
3. The method according to claim 1, wherein the solvent I is at least one selected from benzene, toluene, methylene chloride, N-dimethylformamide, dimethyl sulfoxide.
4. A process according to any one of claims 1-3, wherein the conditions of the contact reaction at least satisfy: the temperature is 20-150 ℃.
5. The method according to claim 1, wherein the compound represented by the formula (II-1), the compound represented by the formula (II-2) and the acid-binding agent I are used in a molar ratio of 1: (1-10): (1-10).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011622775.4A CN112661668B (en) | 2020-12-31 | 2020-12-31 | N-substituted amide compound and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011622775.4A CN112661668B (en) | 2020-12-31 | 2020-12-31 | N-substituted amide compound and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112661668A CN112661668A (en) | 2021-04-16 |
| CN112661668B true CN112661668B (en) | 2023-07-28 |
Family
ID=75412166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011622775.4A Active CN112661668B (en) | 2020-12-31 | 2020-12-31 | N-substituted amide compound and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112661668B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114989142A (en) * | 2022-05-09 | 2022-09-02 | 沈阳万菱生物技术有限公司 | A kind of preparation method of pyrazole compounds |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1245487A (en) * | 1997-01-03 | 2000-02-23 | 巴斯福股份公司 | 3-aminocarbonyl/1-aminothiocarbonyl-substituted 2-benzoyl-cyclohexan-1,3-diones with herbicidal effect |
| CN101983191A (en) * | 2008-02-01 | 2011-03-02 | 武田药品工业株式会社 | Oxim derivatives as hsp90 inhibitors |
| CN103467470A (en) * | 2013-09-11 | 2013-12-25 | 中国科学院化学研究所 | Ocycloimino sugar compound and intermediate, medicament, preparation method and application thereof |
-
2020
- 2020-12-31 CN CN202011622775.4A patent/CN112661668B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1245487A (en) * | 1997-01-03 | 2000-02-23 | 巴斯福股份公司 | 3-aminocarbonyl/1-aminothiocarbonyl-substituted 2-benzoyl-cyclohexan-1,3-diones with herbicidal effect |
| CN101983191A (en) * | 2008-02-01 | 2011-03-02 | 武田药品工业株式会社 | Oxim derivatives as hsp90 inhibitors |
| CN103467470A (en) * | 2013-09-11 | 2013-12-25 | 中国科学院化学研究所 | Ocycloimino sugar compound and intermediate, medicament, preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112661668A (en) | 2021-04-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO340420B1 (en) | Process for the preparation of 1- (3- (2- (1-benzothiophen-5-yl) -ethoxy) propyl) azetidin-3-ol or salts thereof | |
| AU2013225123B2 (en) | Process for the preparation of phenyl substituted 3 - difluoromethyl - 1 -methyl - 1H - pyrazole - 4 - carboxylic n-methoxy- [1 -methyl- 2 - phenylethyl] amides | |
| IE930475A1 (en) | Process for the preparation of¹N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propylamine¹and acid addition salts thereof | |
| CN112544621B (en) | Method for preparing 2- (4-chlorophenoxy) -propoxyamine | |
| EP3724162B1 (en) | Intermediates for optically active piperidine derivatives and preparation methods thereof | |
| HU228204B1 (en) | New process for the preparation of 11-amino-3-chloro-6,11-dihydro-5,5-dioxo-6-methyl-dibenzo[c,f][1,2]thiazepine and use thereof for the synthesis of tianeptine | |
| CN112661668B (en) | N-substituted amide compound and preparation method thereof | |
| EP1773783B1 (en) | Method for preparing n-piperidino-1,5-diphenylpyrazole-3-carboxamide derivatives | |
| KR20050086927A (en) | 1-alkyl-3-aminoindazoles | |
| Vasilevsky et al. | Ethyl vinyl ether--an agent for protection of the pyrazole NH-fragment. A convenient method for the preparation of N-unsubstituted 4-Alkynylpyrazoles | |
| CN115197261B (en) | Synthesis method of oxadiazine boron derivative | |
| IL103229A (en) | Imidazolylmethyl-pyridine derivatives their preparation and pharmaceutical compositions containing them | |
| JP2001521498A (en) | Method for producing O- (3-amino-2-hydroxy-propyl) -hydroxymic acid halide | |
| Bossard et al. | New indium-mediated reactions of enamines | |
| EP1367052B1 (en) | Intermediate for the preparation of carvedilol | |
| CN111848423B (en) | Preparation method of tert-butyl 3-oxocyclobutylcarbamate | |
| CN110724098A (en) | Synthetic method of 5, 7-dichloro-1, 2,3, 4-tetrahydroisoquinoline-6-carboxylic acid hydrochloride | |
| CN111892547A (en) | Synthesis method of prothioconazole intermediate | |
| JPH02149550A (en) | N-(2-carboxy-3',4'-dimethoxy-cynnamoyl)-anthranilic acid, and production thereof | |
| CA1052383A (en) | Process for the production of 1,2,4-triazole derivatives | |
| JP2003508521A (en) | Method for producing 1-substituted 5-hydroxymethylimidazole | |
| EP3741745B1 (en) | Method for producing n-alkoxycarbonylpiperidine derivative, and intermediate therefor | |
| CN110494417B (en) | Production of N-substituted aromatic hydroxylamines | |
| JP2002155058A (en) | Method for producing 1-substituted hydratoin compound | |
| KR101390486B1 (en) | Method for the synthesis of n-[3-[(2-methoxyphenyl)sulfanyl]-2-methylpropyl]-3,4-dihydro-2h-1,5-benzoxathiepin-3-amine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |