NO862233L - Fremgangsmaate ved fremstilling av imidazoquinazolinderivater. - Google Patents

Fremgangsmaate ved fremstilling av imidazoquinazolinderivater.

Info

Publication number: NO862233L
Authority: NO; Norway
Prior art keywords: formula; compound; het; amino; solution
Prior art date: 1985-06-05

Application number

NO862233A

Other languages

English (en)

Norwegian (no)

Other versions

NO862233D0 (no

Inventor

Simon Fraser Campbell

David Anthony Roberts

Original Assignee

Pfizer

Priority date (The priority date 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 date listed.)

1985-06-05

Filing date

1986-06-04

Publication date

1986-12-08

1985-06-05 Priority claimed from GB858514207A external-priority patent/GB8514207D0/en

1985-11-05 Priority claimed from GB858527208A external-priority patent/GB8527208D0/en

1986-06-04 Application filed by Pfizer filed Critical Pfizer

1986-06-04 Publication of NO862233D0 publication Critical patent/NO862233D0/no

1986-12-08 Publication of NO862233L publication Critical patent/NO862233L/no

Links

238000002360 preparation method Methods 0.000 title claims description 26
238000000034 method Methods 0.000 title claims description 18
KJMFQJFNQYWQAV-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinazoline Chemical class C1=NC=NC2=C(NC=N3)C3=CC=C21 KJMFQJFNQYWQAV-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 77
239000000203 mixture Substances 0.000 claims description 57
238000004519 manufacturing process Methods 0.000 claims description 39
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 34
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
-1 hydroxy, hydroxymethyl Chemical group 0.000 claims description 30
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 19
229910000029 sodium carbonate Inorganic materials 0.000 claims description 16
238000006243 chemical reaction Methods 0.000 claims description 14
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical compound C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 claims description 13
JIAARYAFYJHUJI-UHFFFAOYSA-L Zinc chloride Inorganic materials [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 13
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
229910052757 nitrogen Inorganic materials 0.000 claims description 11
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 11
235000005074 zinc chloride Nutrition 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
238000010438 heat treatment Methods 0.000 claims description 7
239000011592 zinc chloride Substances 0.000 claims description 7
125000002883 imidazolyl group Chemical group 0.000 claims description 6
239000003960 organic solvent Substances 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
125000001425 triazolyl group Chemical group 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
238000011282 treatment Methods 0.000 claims description 5
125000001401 1,2,4-triazol-4-yl group Chemical group N=1N=C([H])N([*])C=1[H] 0.000 claims description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
229910052740 iodine Inorganic materials 0.000 claims description 4
125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 3
239000003054 catalyst Substances 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
150000001204 N-oxides Chemical class 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
125000001786 isothiazolyl group Chemical group 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
125000002098 pyridazinyl group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
238000002425 crystallisation Methods 0.000 claims 3
230000008025 crystallization Effects 0.000 claims 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
238000002156 mixing Methods 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 72
239000000243 solution Substances 0.000 description 67
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 59
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
239000007787 solid Substances 0.000 description 31
238000004458 analytical method Methods 0.000 description 28
239000000377 silicon dioxide Substances 0.000 description 28
238000001704 evaporation Methods 0.000 description 27
230000008020 evaporation Effects 0.000 description 25
238000010992 reflux Methods 0.000 description 24
239000003921 oil Substances 0.000 description 23
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
239000000284 extract Substances 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
239000008346 aqueous phase Substances 0.000 description 16
239000007858 starting material Substances 0.000 description 16
239000000463 material Substances 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
239000000725 suspension Substances 0.000 description 10
DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
238000003756 stirring Methods 0.000 description 9
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
241000282472 Canis lupus familiaris Species 0.000 description 5
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
239000002253 acid Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
239000001632 sodium acetate Substances 0.000 description 5
235000017281 sodium acetate Nutrition 0.000 description 5
230000002861 ventricular Effects 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 4
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
235000011114 ammonium hydroxide Nutrition 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
239000010779 crude oil Substances 0.000 description 4
ULOLIZHBYWAICY-UHFFFAOYSA-N ethyl 2-(benzylamino)acetate Chemical class CCOC(=O)CNCC1=CC=CC=C1 ULOLIZHBYWAICY-UHFFFAOYSA-N 0.000 description 4
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
UAWVZBDVSNLPDT-UHFFFAOYSA-N methyl 2-(benzylamino)acetate Chemical class COC(=O)CNCC1=CC=CC=C1 UAWVZBDVSNLPDT-UHFFFAOYSA-N 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 4
OWROQSJHLIWNMW-UHFFFAOYSA-N 1-(3-methyl-4-nitrophenyl)-1,2,4-triazole Chemical compound C1=C([N+]([O-])=O)C(C)=CC(N2N=CN=C2)=C1 OWROQSJHLIWNMW-UHFFFAOYSA-N 0.000 description 3
SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 3
XWMQLIUJOLXRRV-UHFFFAOYSA-N 2,4-dimethyl-1-(3-methyl-4-nitrophenyl)imidazole Chemical compound CC1=NC(C)=CN1C1=CC=C([N+]([O-])=O)C(C)=C1 XWMQLIUJOLXRRV-UHFFFAOYSA-N 0.000 description 3
LLPKQRMDOFYSGZ-UHFFFAOYSA-N 2,5-dimethyl-1h-imidazole Chemical compound CC1=CN=C(C)N1 LLPKQRMDOFYSGZ-UHFFFAOYSA-N 0.000 description 3
WAMPTKWYINJLIV-UHFFFAOYSA-N 2-iodo-6-methyl-4-(1,2,4-triazol-4-yl)aniline Chemical compound IC1=C(N)C(C)=CC(N2C=NN=C2)=C1 WAMPTKWYINJLIV-UHFFFAOYSA-N 0.000 description 3
YOQDUDBMJMEGMN-UHFFFAOYSA-N 2-methyl-4-(1,2,4-triazol-1-yl)aniline Chemical compound C1=C(N)C(C)=CC(N2N=CN=C2)=C1 YOQDUDBMJMEGMN-UHFFFAOYSA-N 0.000 description 3
KFXBWHFKOWWYJB-UHFFFAOYSA-N 2-methyl-4-(1,2,4-triazol-4-yl)aniline Chemical compound C1=C(N)C(C)=CC(N2C=NN=C2)=C1 KFXBWHFKOWWYJB-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 3
206010019280 Heart failures Diseases 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
239000002585 base Substances 0.000 description 3
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
230000008602 contraction Effects 0.000 description 3
238000001816 cooling Methods 0.000 description 3
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
150000002466 imines Chemical class 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
230000002107 myocardial effect Effects 0.000 description 3
230000009090 positive inotropic effect Effects 0.000 description 3
238000000746 purification Methods 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
238000001665 trituration Methods 0.000 description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
ZODQWFPDKBKNTF-UHFFFAOYSA-N 2-(bromomethyl)-4-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1CBr ZODQWFPDKBKNTF-UHFFFAOYSA-N 0.000 description 2
UIKUJTQGSVGAGP-UHFFFAOYSA-N 2-amino-3-methyl-5-(1,2,4-triazol-4-yl)benzaldehyde Chemical compound O=CC1=C(N)C(C)=CC(N2C=NN=C2)=C1 UIKUJTQGSVGAGP-UHFFFAOYSA-N 0.000 description 2
JIYZJPGPTQJASU-UHFFFAOYSA-N 2-amino-3-methyl-5-(1,2,4-triazol-4-yl)benzonitrile Chemical compound N#CC1=C(N)C(C)=CC(N2C=NN=C2)=C1 JIYZJPGPTQJASU-UHFFFAOYSA-N 0.000 description 2
FMVAHKTXFRGJIR-UHFFFAOYSA-N 2-amino-3-methyl-5-(6-oxo-1h-pyridin-3-yl)benzaldehyde Chemical compound O=CC1=C(N)C(C)=CC(C=2C=NC(O)=CC=2)=C1 FMVAHKTXFRGJIR-UHFFFAOYSA-N 0.000 description 2
IVWORXPNANEBDD-UHFFFAOYSA-N 2-amino-5-(2,4-dimethylimidazol-1-yl)-3-methylbenzaldehyde Chemical compound CC1=NC(C)=CN1C1=CC(C)=C(N)C(C=O)=C1 IVWORXPNANEBDD-UHFFFAOYSA-N 0.000 description 2
YCWKMHJNEVUVKN-UHFFFAOYSA-N 2-amino-5-(2,4-dimethylimidazol-1-yl)-3-methylbenzonitrile Chemical compound CC1=NC(C)=CN1C1=CC(C)=C(N)C(C#N)=C1 YCWKMHJNEVUVKN-UHFFFAOYSA-N 0.000 description 2
RKUOXNWQAPGCCF-UHFFFAOYSA-N 2-amino-5-(6-methoxypyridin-3-yl)-3-methylbenzaldehyde Chemical compound C1=NC(OC)=CC=C1C1=CC(C)=C(N)C(C=O)=C1 RKUOXNWQAPGCCF-UHFFFAOYSA-N 0.000 description 2
YKULPUZMSGPMSV-UHFFFAOYSA-N 2-amino-5-iodo-3-methylbenzaldehyde Chemical compound CC1=CC(I)=CC(C=O)=C1N YKULPUZMSGPMSV-UHFFFAOYSA-N 0.000 description 2
WFKOJKHXWWNXPK-UHFFFAOYSA-N 2-amino-5-iodo-3-methylbenzoic acid Chemical compound CC1=CC(I)=CC(C(O)=O)=C1N WFKOJKHXWWNXPK-UHFFFAOYSA-N 0.000 description 2
TUJVGHCSNXCAFE-UHFFFAOYSA-N 3-bromo-2,6-dimethylpyridine Chemical compound CC1=CC=C(Br)C(C)=N1 TUJVGHCSNXCAFE-UHFFFAOYSA-N 0.000 description 2
MCXPFFNKSUZDRO-UHFFFAOYSA-N 4-(2,4-dimethylimidazol-1-yl)-2-methylaniline Chemical compound CC1=NC(C)=CN1C1=CC=C(N)C(C)=C1 MCXPFFNKSUZDRO-UHFFFAOYSA-N 0.000 description 2
JCGZHGMBEQIYEY-UHFFFAOYSA-N 4-(3-methyl-4-nitrophenyl)-1,2,4-triazole Chemical compound C1=C([N+]([O-])=O)C(C)=CC(N2C=NN=C2)=C1 JCGZHGMBEQIYEY-UHFFFAOYSA-N 0.000 description 2
JHFOWEGCZWLHNW-UHFFFAOYSA-N 4-fluoro-2-methyl-1-nitrobenzene Chemical compound CC1=CC(F)=CC=C1[N+]([O-])=O JHFOWEGCZWLHNW-UHFFFAOYSA-N 0.000 description 2
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
206010007559 Cardiac failure congestive Diseases 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
241000287181 Sturnus vulgaris Species 0.000 description 2
YSVZGWAJIHWNQK-UHFFFAOYSA-N [3-(hydroxymethyl)-2-bicyclo[2.2.1]heptanyl]methanol Chemical compound C1CC2C(CO)C(CO)C1C2 YSVZGWAJIHWNQK-UHFFFAOYSA-N 0.000 description 2
239000000654 additive Substances 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000002775 capsule Substances 0.000 description 2
210000001715 carotid artery Anatomy 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
150000001805 chlorine compounds Chemical class 0.000 description 2
238000009109 curative therapy Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
WHJBDRZQZBLTBQ-UHFFFAOYSA-N ethyl 2-[(2-amino-5-iodophenyl)methylamino]acetate Chemical compound CCOC(=O)CNCC1=CC(I)=CC=C1N WHJBDRZQZBLTBQ-UHFFFAOYSA-N 0.000 description 2
WTLOQQAQDPHWMD-UHFFFAOYSA-N ethyl 2-[(2-aminophenyl)methylamino]acetate Chemical compound CCOC(=O)CNCC1=CC=CC=C1N WTLOQQAQDPHWMD-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
125000001475 halogen functional group Chemical group 0.000 description 2
208000019622 heart disease Diseases 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
230000000297 inotrophic effect Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
NSOKPFGRYHIKTO-UHFFFAOYSA-N methyl 2-[[2-amino-5-(2,4-dimethylimidazol-1-yl)phenyl]methylamino]acetate Chemical compound C1=C(N)C(CNCC(=O)OC)=CC(N2C(=NC(C)=C2)C)=C1 NSOKPFGRYHIKTO-UHFFFAOYSA-N 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
230000037361 pathway Effects 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
238000011176 pooling Methods 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
239000002904 solvent Substances 0.000 description 2
230000004936 stimulating effect Effects 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
239000003039 volatile agent Substances 0.000 description 2
125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 description 1
MWZDIEIXRBWPLG-UHFFFAOYSA-N 1-methyl-1,2,4-triazole Chemical compound CN1C=NC=N1 MWZDIEIXRBWPLG-UHFFFAOYSA-N 0.000 description 1
WNAJXPYVTFYEST-UHFFFAOYSA-N 2-Amino-3-methylbenzoate Chemical compound CC1=CC=CC(C(O)=O)=C1N WNAJXPYVTFYEST-UHFFFAOYSA-N 0.000 description 1
ZROXUHQDNXAJRA-UHFFFAOYSA-N 2-amino-3-methyl-5-(1,2,4-triazol-1-yl)benzaldehyde Chemical compound O=CC1=C(N)C(C)=CC(N2N=CN=C2)=C1 ZROXUHQDNXAJRA-UHFFFAOYSA-N 0.000 description 1
SMHAFJGWSMTKON-UHFFFAOYSA-N 2-amino-3-methyl-5-(1,2,4-triazol-1-yl)benzonitrile Chemical compound N#CC1=C(N)C(C)=CC(N2N=CN=C2)=C1 SMHAFJGWSMTKON-UHFFFAOYSA-N 0.000 description 1
ONXVKRQZYPIRQJ-UHFFFAOYSA-N 2-amino-3-methylbenzaldehyde Chemical compound CC1=CC=CC(C=O)=C1N ONXVKRQZYPIRQJ-UHFFFAOYSA-N 0.000 description 1
RPSMHRWKUQIEBQ-UHFFFAOYSA-N 2-bromo-4-(2,4-dimethylimidazol-1-yl)-6-methylaniline Chemical compound CC1=NC(C)=CN1C1=CC(C)=C(N)C(Br)=C1 RPSMHRWKUQIEBQ-UHFFFAOYSA-N 0.000 description 1
SNZAOEXWIMBEFE-UHFFFAOYSA-N 2-iodo-6-methyl-4-(1,2,4-triazol-1-yl)aniline Chemical compound IC1=C(N)C(C)=CC(N2N=CN=C2)=C1 SNZAOEXWIMBEFE-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
XPAYEWBTLKOEDA-UHFFFAOYSA-N 3-methyl-4-nitroaniline Chemical compound CC1=CC(N)=CC=C1[N+]([O-])=O XPAYEWBTLKOEDA-UHFFFAOYSA-N 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
XADICJHFELMBGX-UHFFFAOYSA-N 5-bromo-2-methoxypyridine Chemical compound COC1=CC=C(Br)C=N1 XADICJHFELMBGX-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
101100495531 Caenorhabditis elegans cgh-1 gene Proteins 0.000 description 1
241000282465 Canis Species 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
208000020446 Cardiac disease Diseases 0.000 description 1
206010007556 Cardiac failure acute Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
241000282412 Homo Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
238000004566 IR spectroscopy Methods 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
DLUUHJHVZBQFQQ-UHFFFAOYSA-N [2-amino-5-(6-methoxypyridin-3-yl)-3-methylphenyl]methanol Chemical compound C1=NC(OC)=CC=C1C1=CC(C)=C(N)C(CO)=C1 DLUUHJHVZBQFQQ-UHFFFAOYSA-N 0.000 description 1
YXUVQQDLYINJIN-UHFFFAOYSA-M [Cl-].CC1=NC(=CC=C1[Zn+])C Chemical compound [Cl-].CC1=NC(=CC=C1[Zn+])C YXUVQQDLYINJIN-UHFFFAOYSA-M 0.000 description 1
BLVCCVPMWIDMAH-UHFFFAOYSA-M [Cl-].CN1N=CN=C1[Zn+] Chemical compound [Cl-].CN1N=CN=C1[Zn+] BLVCCVPMWIDMAH-UHFFFAOYSA-M 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
229910000272 alkali metal oxide Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
239000000496 cardiotonic agent Substances 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
VWOQSIOHOUWUAL-UHFFFAOYSA-N chloroform methane Chemical compound [H]C[H].ClC(Cl)Cl.ClC(Cl)Cl VWOQSIOHOUWUAL-UHFFFAOYSA-N 0.000 description 1
WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
238000004040 coloring Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
230000001351 cycling effect Effects 0.000 description 1
YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
HQEMRUUXLOWFRF-UHFFFAOYSA-N ethyl 2-[(5-fluoro-2-nitrophenyl)methyl-(2,2,2-trifluoroacetyl)amino]acetate Chemical compound CCOC(=O)CN(C(=O)C(F)(F)F)CC1=CC(F)=CC=C1[N+]([O-])=O HQEMRUUXLOWFRF-UHFFFAOYSA-N 0.000 description 1
KJOVSVHYOCTJPP-UHFFFAOYSA-N ethyl 2-[(5-fluoro-2-nitrophenyl)methylamino]acetate Chemical compound CCOC(=O)CNCC1=CC(F)=CC=C1[N+]([O-])=O KJOVSVHYOCTJPP-UHFFFAOYSA-N 0.000 description 1
LDZSKTNIRISNLD-UHFFFAOYSA-N ethyl 2-[[2-amino-3-methyl-5-(1,2,4-triazol-1-yl)phenyl]methylamino]acetate Chemical compound CC1=C(N)C(CNCC(=O)OCC)=CC(N2N=CN=C2)=C1 LDZSKTNIRISNLD-UHFFFAOYSA-N 0.000 description 1
KAOBHTYAIFPBSO-UHFFFAOYSA-N ethyl 2-[[2-amino-3-methyl-5-(6-oxo-1h-pyridin-3-yl)phenyl]methylamino]acetate Chemical compound CC1=C(N)C(CNCC(=O)OCC)=CC(C=2C=NC(O)=CC=2)=C1 KAOBHTYAIFPBSO-UHFFFAOYSA-N 0.000 description 1
SHBURHYWFWUJMY-UHFFFAOYSA-N ethyl 2-[[2-amino-5-(1,2,4-triazol-1-yl)phenyl]methyl-(2,2,2-trifluoroacetyl)amino]acetate Chemical compound C1=C(N)C(CN(CC(=O)OCC)C(=O)C(F)(F)F)=CC(N2N=CN=C2)=C1 SHBURHYWFWUJMY-UHFFFAOYSA-N 0.000 description 1
UMTQBHKVOIJNDE-UHFFFAOYSA-N ethyl 2-[[2-amino-5-(2,4-dimethylimidazol-1-yl)phenyl]methyl-(2,2,2-trifluoroacetyl)amino]acetate Chemical compound C1=C(N)C(CN(CC(=O)OCC)C(=O)C(F)(F)F)=CC(N2C(=NC(C)=C2)C)=C1 UMTQBHKVOIJNDE-UHFFFAOYSA-N 0.000 description 1
KUTALVPLCOKRJZ-UHFFFAOYSA-N ethyl 2-[[2-nitro-5-(1,2,4-triazol-1-yl)phenyl]methyl-(2,2,2-trifluoroacetyl)amino]acetate Chemical compound C1=C([N+]([O-])=O)C(CN(CC(=O)OCC)C(=O)C(F)(F)F)=CC(N2N=CN=C2)=C1 KUTALVPLCOKRJZ-UHFFFAOYSA-N 0.000 description 1
ZKWBVOBQLWTJLQ-UHFFFAOYSA-N ethyl 2-[[5-(2,4-dimethylimidazol-1-yl)-2-nitrophenyl]methyl-(2,2,2-trifluoroacetyl)amino]acetate Chemical compound C1=C([N+]([O-])=O)C(CN(CC(=O)OCC)C(=O)C(F)(F)F)=CC(N2C(=NC(C)=C2)C)=C1 ZKWBVOBQLWTJLQ-UHFFFAOYSA-N 0.000 description 1
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
238000006138 lithiation reaction Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
150000002641 lithium Chemical class 0.000 description 1
UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
WBCWBUVVMOPLIS-UHFFFAOYSA-N methyl 2-[[2-amino-5-(1,2,4-triazol-1-yl)phenyl]methylamino]acetate Chemical compound C1=C(N)C(CNCC(=O)OC)=CC(N2N=CN=C2)=C1 WBCWBUVVMOPLIS-UHFFFAOYSA-N 0.000 description 1
HMZHEECHJWHZJX-UHFFFAOYSA-N methyl 2-amino-2-methylpropanoate Chemical compound COC(=O)C(C)(C)N HMZHEECHJWHZJX-UHFFFAOYSA-N 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
POVXOWVFLAAVBH-UHFFFAOYSA-N n-formamidoformamide Chemical compound O=CNNC=O POVXOWVFLAAVBH-UHFFFAOYSA-N 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
CZAAKPFIWJXPQT-UHFFFAOYSA-N quinazolin-2-amine Chemical compound C1=CC=CC2=NC(N)=NC=C21 CZAAKPFIWJXPQT-UHFFFAOYSA-N 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
238000010792 warming Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

NO862233A 1985-06-05 1986-06-04 Fremgangsmaate ved fremstilling av imidazoquinazolinderivater. NO862233L (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB858514207A GB8514207D0 (en)	1985-06-05	1985-06-05	Cardiac stimulants
GB858527208A GB8527208D0 (en)	1985-11-05	1985-11-05	Cardiac stimulants

Publications (2)

Publication Number	Publication Date
NO862233D0 NO862233D0 (no)	1986-06-04
NO862233L true NO862233L (no)	1986-12-08

Family

ID=26289332

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO862233A NO862233L (no)	1985-06-05	1986-06-04	Fremgangsmaate ved fremstilling av imidazoquinazolinderivater.

Country Status (16)

Country	Link
US (1)	US4783467A (da)
EP (1)	EP0205280A3 (da)
KR (1)	KR870001362B1 (da)
CN (1)	CN86103833A (da)
AU (1)	AU562773B2 (da)
CA (1)	CA1270486A (da)
DK (1)	DK262486A (da)
ES (2)	ES8708139A1 (da)
FI (1)	FI862375A (da)
GR (1)	GR861425B (da)
HU (1)	HU196408B (da)
IL (1)	IL79003A0 (da)
NO (1)	NO862233L (da)
NZ (1)	NZ216386A (da)
PT (1)	PT82702B (da)
YU (1)	YU95186A (da)

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* Cited by examiner, † Cited by third party
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US4783467A (en) *	1985-06-05	1988-11-08	Pfizer Inc.	Tetrahydroimidazoquinazolinone inotropic agents
CA2113115A1 (en) *	1991-07-29	1993-02-18	Vlad E. Gregor	Quinazoline derivatives as acetylcholinesterase inhibitors
US7700608B2 (en)	2004-08-04	2010-04-20	Shire Holdings Ag	Quinazoline derivatives and their use in the treatment of thrombocythemia
US8426429B2 (en) *	2004-08-06	2013-04-23	Jansssen Pharmaceutica N.V.	2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE)
US8383637B2 (en) *	2004-08-06	2013-02-26	Jansssen Pharmaceutica N.V.	2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE)
US8436006B2 (en) *	2004-08-06	2013-05-07	Jansssen Pharmaceutica N.V.	2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE)
US7910597B2 (en)	2006-11-28	2011-03-22	Shire Llc	Substituted quinazolines
US8304420B2 (en)	2006-11-28	2012-11-06	Shire Llc	Substituted quinazolines for reducing platelet count
WO2022199627A1 (en) *	2021-03-23	2022-09-29	National Institute Of Biological Sciences, Beijing	Polycyclic compounds and uses thereof

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3932407A (en) *	1973-11-19	1976-01-13	Bristol-Myers Company	Optionally substituted 1,2,3,5-tetrahydroimidezo(2,1-b)-quinazolin-2-ones and 6(H)-1,2,3,4-tetrahydropyimido(2,1-b)quinazolin-2-ones
US3983120A (en) *	1974-11-06	1976-09-28	Bristol-Myers Company	Process for the preparation of optionally substituted 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-ones
US3983119A (en) *	1974-11-06	1976-09-28	Bristol-Myers Company	Process for the preparation of optionally substituted 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-ones
NL7807507A (nl) *	1977-07-25	1979-01-29	Hoffmann La Roche	Tricyclische verbindingen.
US4208521A (en) *	1978-07-31	1980-06-17	Bristol-Myers Company	Process for the preparation of imidazo[2,1-b]quinazolinones
CA1131631A (en) *	1979-06-20	1982-09-14	Madhukar S. Chodnekar	Quinazoline derivatives and pharmaceutical preparations
EP0054180A3 (de) *	1980-12-16	1982-12-01	F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft	Verfahren zur Herstellung eines Imidazochinazolinonderivates
JPS604186A (ja) *	1983-06-21	1985-01-10	Dai Ichi Seiyaku Co Ltd	イミダゾキナゾリン化合物
JPS6028979A (ja) *	1983-07-14	1985-02-14	Dai Ichi Seiyaku Co Ltd	イミダゾキナゾリン類化合物
US4593029A (en) *	1984-02-15	1986-06-03	Syntex (U.S.A.) Inc.	Novel ω-(N-imidazolyl)alkyl ethers of 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-ones
US4783467A (en) *	1985-06-05	1988-11-08	Pfizer Inc.	Tetrahydroimidazoquinazolinone inotropic agents

1986
- 1986-05-22 US US06/865,693 patent/US4783467A/en not_active Expired - Lifetime
- 1986-05-28 EP EP86304040A patent/EP0205280A3/en not_active Withdrawn
- 1986-06-02 IL IL79003A patent/IL79003A0/xx unknown
- 1986-06-02 GR GR861425A patent/GR861425B/el unknown
- 1986-06-03 YU YU00951/86A patent/YU95186A/xx unknown
- 1986-06-03 NZ NZ216386A patent/NZ216386A/xx unknown
- 1986-06-03 CA CA000510658A patent/CA1270486A/en not_active Expired - Lifetime
- 1986-06-03 PT PT82702A patent/PT82702B/pt not_active IP Right Cessation
- 1986-06-04 KR KR1019860004434A patent/KR870001362B1/ko not_active IP Right Cessation
- 1986-06-04 NO NO862233A patent/NO862233L/no unknown
- 1986-06-04 HU HU862365A patent/HU196408B/hu unknown
- 1986-06-04 AU AU58427/86A patent/AU562773B2/en not_active Ceased
- 1986-06-04 DK DK262486A patent/DK262486A/da not_active Application Discontinuation
- 1986-06-04 FI FI862375A patent/FI862375A/fi not_active Application Discontinuation
- 1986-06-04 ES ES555723A patent/ES8708139A1/es not_active Expired
- 1986-06-05 CN CN198686103833A patent/CN86103833A/zh active Pending
1987
- 1987-02-26 ES ES557427A patent/ES8800224A1/es not_active Expired

Also Published As

Publication number	Publication date
NZ216386A (en)	1988-08-30
PT82702A (en)	1986-07-01
ES557427A0 (es)	1987-10-16
ES8708139A1 (es)	1987-09-16
FI862375A (fi)	1986-12-06
EP0205280A2 (en)	1986-12-17
AU562773B2 (en)	1987-06-18
YU95186A (en)	1988-04-30
CA1270486A (en)	1990-06-19
FI862375A0 (fi)	1986-06-04
ES555723A0 (es)	1987-09-16
US4783467A (en)	1988-11-08
GR861425B (en)	1986-10-02
EP0205280A3 (en)	1988-11-30
DK262486D0 (da)	1986-06-04
DK262486A (da)	1987-02-16
ES8800224A1 (es)	1987-10-16
PT82702B (pt)	1988-12-15
HU196408B (en)	1988-11-28
KR870001362B1 (ko)	1987-07-20
CN86103833A (zh)	1986-12-31
AU5842786A (en)	1986-12-11
HUT41793A (en)	1987-05-28
NO862233D0 (no)	1986-06-04
IL79003A0 (en)	1986-09-30
KR870000338A (ko)	1987-02-17

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EP0475898A1 (de)	1992-03-18	Azacyclische Verbindungen
JP2000256358A (ja)	2000-09-19	ピラゾール誘導体
KR840000421B1 (ko)	1984-04-02	피라졸로 퀴놀린의 제조방법
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NO862233L (no)	1986-12-08	Fremgangsmaate ved fremstilling av imidazoquinazolinderivater.
CZ17988A3 (en)	1993-02-17	BENZOPYRAN(4,3-c)PYRAZOLE OR BENZOTHIOPYRAN(4,3-c)PYRAZOLE DERIVATIVES, PROCESSES OF THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS IN WHICH THEY ARE COMPRISED
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FI72974C (fi)	1987-08-10	Foerfarande foer framstaellning av terapeutiskt anvaendbara imidazolylpyridiner.
SK46793A3 (en)	1994-02-02	Regenarative melting tank and method of working
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FR2639944A1 (fr)	1990-06-08	Nouveaux derives de l'indole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
JPS61282385A (ja)	1986-12-12	テトラヒドロイミダゾキナゾリノン強心剤