Piquindone((-)-enantiomer), Ro-221319
匹喹酮 Chemical Name: (-)-2,6-Dimethyl-3-ethyl-4,4a,5,6,7,8,8a,9-octahydro-4a,8a-trans-1H-pyrrolo[2,3-g]isoquinolin-4-one; trans-(-)-3-Ethyl-1,4a,5,6,7,8,8a,9-octahydro-2,6-dimethyl-4H-pyrrolo[2,3-g]isoquinolin-4-one
CAS No. 75689-88-2 (monoHCl), 78541-97-6 (racemate), 83784-19-4 (racemic, monoHCl, dihydrate)
项目整合开发状态: Biological Testing
项目研究机构: Roche (Originator)
合成路线:This compound can be prepared by two related ways:1) The reaction of (3,5-dimethoxyphenyl)ethylamine (I) with ethyl chlorocarbonate (A) in CH2Cl2 gives ethyl N-[2-(3,5-dimethoxyphenyl)ethyl]carbamate (II),which is reduced with sodium dihydro-bis(2-methoxyethyl)aluminate in THF yielding N-methyl-(3,5-dimethoxyphenyl)ethylamine (III).Partial hydrogenation of (III) with Li in dry NH3 affords N-methyl-1,5-dimethoxycyclohexa-1,4-diene-3-ethylamine (IV),which is hydrolyzed with refluxing aqueous acetic acid giving 3-[2-(methylamino)ethyl]cyclohexane-1,5-dione (V).The cyclocondensation of (V) with 2-amino-3-pentanone (VI) [prepared by reduction with Zn of 2-isonitroso-3-pentanone (VII)] in refluxing acetic acid yields 6-[2-(N-methylamino)ethyl]-2-methyl-3-ethyl-6,7-dihydro-(5H)-4(1H,5H)indolone (VIII).Finally,this compound is cyclized again with formaldehyde in refluxing octanol.2) The cyclization of (III) with formaldehyde as before gives 3,4-dihydro-1H-6,8-dimethoxy-2-methylisoquinoline (IX),which is reduced partially with Li in dry NH3 as before yielding 1,2,3,4,4a,7-hexahydro-6,8-dimethoxy-2-methylisoquinoline (X).The hydrolysis of (X) with refluxing acetic acid affords octahydro-2-methylisoquinolin-6,8-dione (XI),which is then cyclized with (VI) as before.The racemic base is resolved by treatment with d-(+)-tartaric acid in methanol and a fractional crystallization.
📌 参考资料/链接：
参考文献标题:Isoquinoline derivs.,process for their preparation,intermediates and pharmaceutical compsns.containing them
文献作者:Berger,L.; Olson,G.L.(F.Hoffmann-La Roche AG)
参考来源:EP 0010661
📄 详细内容
合成路线:This compound can be prepared by two related ways:1) The reaction of (3,5-dimethoxyphenyl)ethylamine (I) with ethyl chlorocarbonate (A) in CH2Cl2 gives ethyl N-[2-(3,5-dimethoxyphenyl)ethyl]carbamate (II),which is reduced with sodium dihydro-bis(2-methoxyethyl)aluminate in THF yielding N-methyl-(3,5-dimethoxyphenyl)ethylamine (III).Partial hydrogenation of (III) with Li in dry NH3 affords N-methyl-1,5-dimethoxycyclohexa-1,4-diene-3-ethylamine (IV),which is hydrolyzed with refluxing aqueous acetic acid giving 3-[2-(methylamino)ethyl]cyclohexane-1,5-dione (V).The cyclocondensation of (V) with 2-amino-3-pentanone (VI) [prepared by reduction with Zn of 2-isonitroso-3-pentanone (VII)] in refluxing acetic acid yields 6-[2-(N-methylamino)ethyl]-2-methyl-3-ethyl-6,7-dihydro-(5H)-4(1H,5H)indolone (VIII).Finally,this compound is cyclized again with formaldehyde in refluxing octanol.2) The cyclization of (III) with formaldehyde as before gives 3,4-dihydro-1H-6,8-dimethoxy-2-methylisoquinoline (IX),which is reduced partially with Li in dry NH3 as before yielding 1,2,3,4,4a,7-hexahydro-6,8-dimethoxy-2-methylisoquinoline (X).The hydrolysis of (X) with refluxing acetic acid affords octahydro-2-methylisoquinolin-6,8-dione (XI),which is then cyclized with (VI) as before.The racemic base is resolved by treatment with d-(+)-tartaric acid in methanol and a fractional crystallization.
参考文献标题:RO-22-1319
文献作者:Serradell,M.N.; Blancafort,P.; Owen,R.T.; Castar,J.
参考来源:Drugs Fut 1983,8(10),869
合成路线:This compound can be prepared by two related ways:1) The reaction of (3,5-dimethoxyphenyl)ethylamine (I) with ethyl chlorocarbonate (A) in CH2Cl2 gives ethyl N-[2-(3,5-dimethoxyphenyl)ethyl]carbamate (II),which is reduced with sodium dihydro-bis(2-methoxyethyl)aluminate in THF yielding N-methyl-(3,5-dimethoxyphenyl)ethylamine (III).Partial hydrogenation of (III) with Li in dry NH3 affords N-methyl-1,5-dimethoxycyclohexa-1,4-diene-3-ethylamine (IV),which is hydrolyzed with refluxing aqueous acetic acid giving 3-[2-(methylamino)ethyl]cyclohexane-1,5-dione (V).The cyclocondensation of (V) with 2-amino-3-pentanone (VI) [prepared by reduction with Zn of 2-isonitroso-3-pentanone (VII)] in refluxing acetic acid yields 6-[2-(N-methylamino)ethyl]-2-methyl-3-ethyl-6,7-dihydro-(5H)-4(1H,5H)indolone (VIII).Finally,this compound is cyclized again with formaldehyde in refluxing octanol.2) The cyclization of (III) with formaldehyde as before gives 3,4-dihydro-1H-6,8-dimethoxy-2-methylisoquinoline (IX),which is reduced partially with Li in dry NH3 as before yielding 1,2,3,4,4a,7-hexahydro-6,8-dimethoxy-2-methylisoquinoline (X).The hydrolysis of (X) with refluxing acetic acid affords octahydro-2-methylisoquinolin-6,8-dione (XI),which is then cyclized with (VI) as before.The racemic base is resolved by treatment with d-(+)-tartaric acid in methanol and a fractional crystallization.
参考文献标题:A dopamine receprtor model and its application in the design of a new class of igid pyrrolo[2,3-g]isoquinoline anti-psychotics
文献作者:Olson,G.L.; Cheung,H.-C.; Morgan,K.D.; Blount,J.F.; Todaro,L.; Berger,L.; Davidson,A.B.; Boff,E.
参考来源:J Med Chem 1981,24(9),1026-34
产品链接: CAS No.78541-97-6›› 产品链接: CAS No.83784-19-4››