发明名称 |
Process for the preparation of anti-ischemic and anti-hypertensive drug amlodipine besylate |
摘要 |
Process for the preparation of anti-ischemic and anti-hypertensive drug amlodipine besylate [2-{(2-aminoethoxy)-methyl-4-(2-chlorophenyl) 3-ethoxy carbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine} benzene sulphonate]. Phthalic anhydride is condensed with monoethanol amine at 150-190° C. The resulting N-(2-hydroxyethyl) phthalimide is coupled with 4-chloroethyl acetoacetate in the presence of sodium hydride in an organic solvent in an inert atmosphere at -11 to -15° C. Ethyl-4-[-2(phthalimido) ethoxy] acetoacetate formed is coupled with orthochloro benzaldehyde in the presence of pyridine salt at 70-90° C. Ethyl-2-(2-chloro benzylidine)4-[-2(phthalimido) ethoxy] acetoacetate fanned is condensed with methyl amino crotonate at 20-40° C. in the presence of acetic acid to form phthaloyl amlodipine [2-(2-Phthalimidoethoxy) methyl-3-carboethoxy 1(chlorophenyl)-S-carbomethoxy-6-methyl-1,4-dihydropyridin] which is purified by dissolving in an organic solvent in the ratio 1:2-1:5 w/v and precipitated by the addition of water at 35-60° C. Purified phthaloyl amlodipine is hydrolysed with methylamine in the presence of a protic solvent at 20-50° C. Amlodipine base [2-(aminoethoxy) methyl-3-carboethoxy-4-(2-chlorophenyl)-5-carbomethoxy-6-methyl-1,4-dihydropyridin] formed is reacted with benzene sulfonic acid. The resulting amlodipine besylate is purified in an organic solvent at 30-70° C. and precipitated by the addition of an insoluble solvent.
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申请公布号 |
US2004044218(A1) |
申请公布日期 |
2004.03.04 |
申请号 |
US20030654814 |
申请日期 |
2003.09.04 |
申请人 |
PUROHIT ARUN KUMAR;DESAI BRAHMADER CHILU;SHETE BALASAHEB DASHRATH;BAGWAN SALIM ABBAS |
发明人 |
PUROHIT ARUN KUMAR;DESAI BRAHMADER CHILU;SHETE BALASAHEB DASHRATH;BAGWAN SALIM ABBAS |
分类号 |
C07D211/82;(IPC1-7):C07D213/46 |
主分类号 |
C07D211/82 |
代理机构 |
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