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Trequinsin hydrochloride, HL-725

盐酸曲林菌素Chemical Name: 9,10-Dimethoxy-2-mesitylimino-3-methyl-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one hydrochloride; 9,10-Dimethoxy-3-methyl-2-(2,4,6-trimethylphenylimino)-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one hydrochloride
CAS No. 78416-81-6
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator), Teikoku Hormone (Originator)
合成路线:HL-725 has been synthesized in a variety of ways:1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II).Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III).The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV).Reaction of (IV) with mesidine (C) afforded HL-725.2) Alternately,the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V),which was then reacted with mesidine to give the mesitylino derivative (VI).Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII),which were separated chromatographcally.3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX).Bischler-Napieralski-type cyclization afforded (II),which was then converted to HL-725 by the appropriate route.
📌 参考资料/链接:
参考文献标题:HL-725
文献作者:Arya,V.P.
参考来源:Drugs Fut 1982,7(6),390

📄 详细内容


合成路线:HL-725 has been synthesized in a variety of ways:1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II).Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III).The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV).Reaction of (IV) with mesidine (C) afforded HL-725.2) Alternately,the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V),which was then reacted with mesidine to give the mesitylino derivative (VI).Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII),which were separated chromatographcally.3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX).Bischler-Napieralski-type cyclization afforded (II),which was then converted to HL-725 by the appropriate route.

参考文献标题:
文献作者:
参考来源:DE 2720085


合成路线:HL-725 has been synthesized in a variety of ways:1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II).Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III).The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV).Reaction of (IV) with mesidine (C) afforded HL-725.2) Alternately,the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V),which was then reacted with mesidine to give the mesitylino derivative (VI).Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII),which were separated chromatographcally.3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX).Bischler-Napieralski-type cyclization afforded (II),which was then converted to HL-725 by the appropriate route.

参考文献标题:
文献作者:Lal,B.; D'Sa,A.
参考来源:33rd Ind Pharm Cong (Dec 21,Jaipur) 1981,16(Suppl.1),


合成路线:HL-725 has been synthesized in a variety of ways:1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II).Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III).The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV).Reaction of (IV) with mesidine (C) afforded HL-725.2) Alternately,the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V),which was then reacted with mesidine to give the mesitylino derivative (VI).Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII),which were separated chromatographcally.3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX).Bischler-Napieralski-type cyclization afforded (II),which was then converted to HL-725 by the appropriate route.

参考文献标题:Trequinsin and its analogs
文献作者:Sas,G.; Blask? G.
参考来源:Drugs Fut 1989,14(11),1083-91


合成路线:HL-725 has been synthesized in a variety of ways:1) 1-Carbamoylmethylene-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (I) was cyclized on treatment with diethylcarbonate (A) to give 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinoline-2,4-dione (II).Methylation of (II) with methyliodide in dimethylformamide in the presence of sodium hydride afforded (III).The N-methyl compound (III) was treated with phosphorous pentasulfide to give the thio compound (IV).Reaction of (IV) with mesidine (C) afforded HL-725.2) Alternately,the compound (II) was reacted with phosphorous oxychloride to yield the chloro compound (V),which was then reacted with mesidine to give the mesitylino derivative (VI).Methylation of (VI) with methyliodide afforded HL-725 and the exo-N-methyl isomer (VII),which were separated chromatographcally.3) 3,4-Dimethoxy-beta-phenethyl bromide (VIII) was reacted with barbituric acid (B) to give the alkylated product (IX).Bischler-Napieralski-type cyclization afforded (II),which was then converted to HL-725 by the appropriate route.
参考文献标题:Trequinsin,a potent antihypertensive vasodilator in the series of 2-(arylimino)-3-alkyl-9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido-[6,1-a]isoquinolin-4-ones
文献作者:de Souza,N.J.; Dadkar,N.K.; Lal,B.; D'Sa,A.; Dohadwalla,A.N.
参考来源:J Med Chem 1984,271470-80


产品链接: CAS No. 78416-81-6››