CA1121817A - Procede relatif aux cyanocarboxamidines et a la quinazoline - Google Patents

Procede relatif aux cyanocarboxamidines et a la quinazoline

Info

Publication number: CA1121817A
Authority: CA; Canada
Prior art keywords: formula; carbon atoms; atoms inclusive; compound; cyano
Prior art date: 1977-09-30
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.): Expired

Application number

CA000365159A

Other languages

English (en)

Inventor

George M. Luke

Ronnie R. Crenshaw

Richard A. Partyka

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb Co

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.)

1977-09-30

Filing date

1980-11-20

Publication date

1982-04-13

1977-09-30 Priority claimed from US05/838,417 external-priority patent/US4138561A/en

1980-11-20 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1980-11-20 Priority to CA000365159A priority Critical patent/CA1121817A/fr

1982-04-13 Application granted granted Critical

1982-04-13 Publication of CA1121817A publication Critical patent/CA1121817A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 71
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 title claims description 11
-1 4-amino-2-(4-substituted-piperazine-1-yl)-quinazolines Chemical class 0.000 claims abstract description 32
238000002360 preparation method Methods 0.000 claims abstract description 17
125000004432 carbon atom Chemical group C* 0.000 claims description 28
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 24
238000007363 ring formation reaction Methods 0.000 claims description 22
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 15
239000002904 solvent Substances 0.000 claims description 13
125000000217 alkyl group Chemical group 0.000 claims description 12
150000001875 compounds Chemical class 0.000 claims description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
150000003246 quinazolines Chemical class 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
239000001257 hydrogen Substances 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 6
125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
229910000041 hydrogen chloride Inorganic materials 0.000 claims description 5
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
150000002431 hydrogen Chemical class 0.000 claims description 4
UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 claims description 4
OGFAWKRXZLGJSK-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-2-(4-nitrophenyl)ethanone Chemical compound OC1=CC(O)=CC=C1C(=O)CC1=CC=C([N+]([O-])=O)C=C1 OGFAWKRXZLGJSK-UHFFFAOYSA-N 0.000 claims description 3
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
239000011968 lewis acid catalyst Substances 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 3
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
239000011593 sulfur Substances 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
125000001544 thienyl group Chemical group 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 10
230000015572 biosynthetic process Effects 0.000 abstract description 5
238000003786 synthesis reaction Methods 0.000 abstract description 4
230000003276 anti-hypertensive effect Effects 0.000 abstract description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 18
239000000243 solution Substances 0.000 description 14
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 11
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
239000000203 mixture Substances 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
239000000463 material Substances 0.000 description 7
229910052698 phosphorus Inorganic materials 0.000 description 7
239000011574 phosphorus Substances 0.000 description 7
239000007787 solid Substances 0.000 description 7
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
238000010992 reflux Methods 0.000 description 6
LHPZZVZPOZPDDB-UHFFFAOYSA-N 4-isothiocyanato-1,2-dimethoxybenzene Chemical compound COC1=CC=C(N=C=S)C=C1OC LHPZZVZPOZPDDB-UHFFFAOYSA-N 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
239000007858 starting material Substances 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
NFKMPKOGCRBAJF-UHFFFAOYSA-N $l^{1}-azanylformonitrile Chemical compound [N]C#N NFKMPKOGCRBAJF-UHFFFAOYSA-N 0.000 description 3
QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 3
NYTBFFZQIRSGLL-UHFFFAOYSA-N 4-isocyanato-1,2-dimethoxybenzene Chemical compound COC1=CC=C(N=C=O)C=C1OC NYTBFFZQIRSGLL-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000004202 carbamide Substances 0.000 description 3
150000003857 carboxamides Chemical class 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000002026 chloroform extract Substances 0.000 description 3
150000001912 cyanamides Chemical class 0.000 description 3
125000004093 cyano group Chemical group *C#N 0.000 description 3
239000007789 gas Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
VBUBADWLHFZFDK-UHFFFAOYSA-N quinazoline;hydrochloride Chemical compound Cl.N1=CN=CC2=CC=CC=C21 VBUBADWLHFZFDK-UHFFFAOYSA-N 0.000 description 3
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
239000000725 suspension Substances 0.000 description 3
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 2
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
244000166102 Eucalyptus leucoxylon Species 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000002220 antihypertensive agent Substances 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
SADPINFEWFPMEA-UHFFFAOYSA-N furan-2-yl(piperazin-1-yl)methanone Chemical compound C=1C=COC=1C(=O)N1CCNCC1 SADPINFEWFPMEA-UHFFFAOYSA-N 0.000 description 2
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
BEBULARNHRENRL-UHFFFAOYSA-N (2-hydroxy-2-methylpropyl) piperazine-1-carboxylate Chemical compound CC(C)(O)COC(=O)N1CCNCC1 BEBULARNHRENRL-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
SDTBJQANMVJMSP-UHFFFAOYSA-N 1,4-diazepan-1-yl(furan-2-yl)methanone Chemical group C=1C=COC=1C(=O)N1CCCNCC1 SDTBJQANMVJMSP-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
OGEPTCLSVFACRT-UHFFFAOYSA-N 1-isothiocyanato-2,3,4-trimethoxybenzene Chemical compound COC1=CC=C(N=C=S)C(OC)=C1OC OGEPTCLSVFACRT-UHFFFAOYSA-N 0.000 description 1
FSKSRCFNVZOYLO-UHFFFAOYSA-N 1-isothiocyanato-2,3-dimethoxybenzene Chemical compound COC1=CC=CC(N=C=S)=C1OC FSKSRCFNVZOYLO-UHFFFAOYSA-N 0.000 description 1
TUQSVSYUEBNNKQ-UHFFFAOYSA-N 2,4-dichloroquinazoline Chemical compound C1=CC=CC2=NC(Cl)=NC(Cl)=C21 TUQSVSYUEBNNKQ-UHFFFAOYSA-N 0.000 description 1
125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 1
UDMYVIOIQWIDRY-UHFFFAOYSA-N 6,7-dimethoxy-2-(4-methylpiperazin-1-yl)quinazolin-4-amine pentachloro-lambda5-phosphane dihydrochloride Chemical compound P(Cl)(Cl)(Cl)(Cl)Cl.Cl.Cl.NC1=NC(=NC2=CC(=C(C=C12)OC)OC)N1CCN(CC1)C UDMYVIOIQWIDRY-UHFFFAOYSA-N 0.000 description 1
LENSZUVXOXHZTL-UHFFFAOYSA-N 6,7-dimethoxy-2-(4-methylpiperazin-1-yl)quinazolin-4-amine;dihydrochloride Chemical compound Cl.Cl.N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N1CCN(C)CC1 LENSZUVXOXHZTL-UHFFFAOYSA-N 0.000 description 1
101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
229910015400 FeC13 Inorganic materials 0.000 description 1
102100039401 Gap junction beta-6 protein Human genes 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
230000009858 acid secretion Effects 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
239000012491 analyte Substances 0.000 description 1
229940051881 anilide analgesics and antipyretics Drugs 0.000 description 1
150000003931 anilides Chemical class 0.000 description 1
230000000767 anti-ulcer Effects 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
159000000032 aromatic acids Chemical class 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
239000002585 base Substances 0.000 description 1
150000001555 benzenes Chemical class 0.000 description 1
230000037396 body weight Effects 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
RYTLGWCJESCDMY-UHFFFAOYSA-N carbamimidoyl chloride Chemical class NC(Cl)=N RYTLGWCJESCDMY-UHFFFAOYSA-N 0.000 description 1
YDVJBLJCSLVMSY-UHFFFAOYSA-N carbamoyl cyanide Chemical class NC(=O)C#N YDVJBLJCSLVMSY-UHFFFAOYSA-N 0.000 description 1
150000001723 carbon free-radicals Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
CJQGSTFFFNJNMC-UHFFFAOYSA-N cyclopentyl(piperazin-1-yl)methanone Chemical compound C1CNCCN1C(=O)C1CCCC1 CJQGSTFFFNJNMC-UHFFFAOYSA-N 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
CCAFPWNGIUBUSD-UHFFFAOYSA-N diethyl sulfoxide Chemical compound CCS(=O)CC CCAFPWNGIUBUSD-UHFFFAOYSA-N 0.000 description 1
238000001035 drying Methods 0.000 description 1
125000006575 electron-withdrawing group Chemical group 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical group 0.000 description 1
150000004050 homopiperazines Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
SLALWQDKKDPPEX-UHFFFAOYSA-N n-(3,4-dimethoxyphenyl)-4-(5-methylsulfanyl-1,3,4-oxadiazole-2-carbonyl)piperazine-1-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)N1CCN(C(=O)C=2OC(SC)=NN=2)CC1 SLALWQDKKDPPEX-UHFFFAOYSA-N 0.000 description 1
WXJRCMMPKPGSGC-UHFFFAOYSA-N n-(3,4-dimethoxyphenyl)-4-(furan-2-carbonyl)piperazine-1-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)N1CCN(C(=O)C=2OC=CC=2)CC1 WXJRCMMPKPGSGC-UHFFFAOYSA-N 0.000 description 1
GNTXMSCWTRRBCZ-UHFFFAOYSA-N n-(3,4-dimethoxyphenyl)-4-methylpiperazine-1-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)N1CCN(C)CC1 GNTXMSCWTRRBCZ-UHFFFAOYSA-N 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 description 1
229960002195 perazine Drugs 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical class O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical class S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 1
150000004885 piperazines Chemical class 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
239000000047 product Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000001187 pylorus Anatomy 0.000 description 1
MCZFAEXAOKERQF-UHFFFAOYSA-N quinazoline-4-carboximidamide Chemical class C1=CC=C2C(C(=N)N)=NC=NC2=C1 MCZFAEXAOKERQF-UHFFFAOYSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
239000011343 solid material Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
150000003585 thioureas Chemical class 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
YNZXWQJZEDLQEG-UHFFFAOYSA-N trimazosin Chemical compound N1=C2C(OC)=C(OC)C(OC)=CC2=C(N)N=C1N1CCN(C(=O)OCC(C)(C)O)CC1 YNZXWQJZEDLQEG-UHFFFAOYSA-N 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA000365159A 1977-09-30 1980-11-20 Procede relatif aux cyanocarboxamidines et a la quinazoline Expired CA1121817A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000365159A CA1121817A (fr)	1977-09-30	1980-11-20	Procede relatif aux cyanocarboxamidines et a la quinazoline

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US838,417		1977-09-30
US05/838,417 US4138561A (en)	1977-09-30	1977-09-30	Cyanocarboxamidines and quinazoline process
CA000311878A CA1121816A (fr)	1977-09-30	1978-09-22	Procede d'obtention de cyanocarboxamidines et de quinazoline
CA000365159A CA1121817A (fr)	1977-09-30	1980-11-20	Procede relatif aux cyanocarboxamidines et a la quinazoline

Publications (1)

Publication Number	Publication Date
CA1121817A true CA1121817A (fr)	1982-04-13

Family

ID=27165875

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000365159A Expired CA1121817A (fr)	1977-09-30	1980-11-20	Procede relatif aux cyanocarboxamidines et a la quinazoline

Country Status (1)

Country	Link
CA (1)	CA1121817A (fr)

1980
- 1980-11-20 CA CA000365159A patent/CA1121817A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1999-04-13	MKEX	Expiry

Publication	Publication Date	Title
CA1121816A (fr)	1982-04-13	Procede d'obtention de cyanocarboxamidines et de quinazoline
US4098788A (en)	1978-07-04	Process for preparing quinazolines
CA1090803A (fr)	1980-12-02	2-piperazinyl-5,7-dimethoxyquinazolines
KR920000761B1 (ko)	1992-01-21	치환된 2-피리미디닐-1-피페라진 유도체의 제조방법
CA2077252C (fr)	2001-04-10	Methodes de fabrication d'urees et de guanidines et composes intermediaires servant a ces syntheses
US3843668A (en)	1974-10-22	Certain 4-substituted amino-2,1,3-benzothiadiozoles
RU2099323C1 (ru)	1997-12-20	Производные гуанидина, способ их получения и фармацевтическая композиция, обладающая гипогликемической активностью
CS207791B2 (en)	1981-08-31	Method of making the derivatives of the thiadiazole
CA1049521A (fr)	1979-02-27	Procede pour la preparation de derives 3,4-dihydro-2(1h)-quinazolinone
GB2151617A (en)	1985-07-24	New aminoguanidine derivatives and a process for the preparation thereof
RU2052452C1 (ru)	1996-01-20	Амидиновые производные бензола и их фармацевтически приемлемые соли
CA1121817A (fr)	1982-04-13	Procede relatif aux cyanocarboxamidines et a la quinazoline
Aly et al.	2004	N‐[4‐(dicyanomethylazo) phenyl]‐2‐saccharin‐2‐ylacetamide in the synthesis of pyridazine and pyrimidine derivatives
US3985785A (en)	1976-10-12	Cyanoethyl acetamidine compounds
Jacobs	1970	The synthesis of o‐Amino‐N‐substituted benzamides and 3‐substituted 2, 4 (1H, 3H)‐quinazolinediones from isatoic anhydride
US2621182A (en)	1952-12-09	Office
CA1243677A (fr)	1988-10-25	Preparation de 4-amino-6,7-dimethoxy-2- [4-(furo-2-yl)-piperazin-1-yl]-quinazoline et ses sels physiologiquement compatibles
US3979397A (en)	1976-09-07	Pharmaceutically effective novel 3,4-dihydro-1,2- and 1,3-thiozolo [4,3a] is
HU191408B (en)	1987-02-27	Process for preparing new imino-thiazolidine derivatives
Mohareb et al.	2000	Reaction of ethyl 2‐diazo‐4, 5, 6, 7‐tetrahydrobenzo [b] thiophene‐3‐carboxylate with 3‐iminobutyronitrile: synthesis of pyridazines, thiophenes, and their fused derivatives
US4014884A (en)	1977-03-29	Basically substituted 3,4-dihydro-2H-isoquinolin-1-thiones
EP0693055A1 (fr)	1996-01-24	Nouveau procede de preparation de derives de clonidine
DE2857087A1 (de)	1980-12-04	Cyanocarboxamidines and quinazoline process
US2535971A (en)	1950-12-26	1-carbalkoxy-4-substituted piperazines
CA1071652A (fr)	1980-02-12	Les styrylamidines