【药物名称】Captopril, SQ-14225, Captril, Cesplon, Tensiomin, Capoten
化学结构式(Chemical Structure):
参考文献No.201791
标题:Captopril
作者:Roberts, P.J.; Casta馿r, J.
来源:Drugs Fut 1978,3(11),795
合成路线图解说明:

It is prepared by hydrolysis with ammonia in methanol of N-(3-acetylthio-2-methylpropanoyl)-L-proline (I). Compound (I) can be obtained in three different ways: 1) The reaction of L-proline tert-butyl ester (II) with 3-acetylthio-2-methyl-propanoic acid (III) by means of dicyclohexylcarbodiimide in CH2Cl2 gives N-(3-acetylthio-2-methylpropanoyl)-L-proline tert-butyl ester (IV), which is hydrolyzed with trifluoroacetic acid in anisole. 2) By condensation of L-proline (V) with 3-acetylthio-2-methylpropanoyl chloride (VI) (prepared from the corresponding acid (III) with SOCl2) by means of NaOH in water. 3) The condensation of L-proline (V) with methacryloyl chloride (VII) by means of NaHCO3 in water yields N-methacryloyl-L-proline (VIII), which is then treated with thiolacetic acid (A) and azobisisobutyronitrile. The acid (III) is obtained by addition of thiolacetic acid (IX) to methacrylic acid (X) at 100 C.

参考文献No.701042
标题:Azetidine-2-carboxylic acid derivatives
作者:Cushman, D.W.; Ondetti, M.A.
来源:BE 0851361; DD 283999; JP 58189113; JP 58189158; US 4046889; US 4154840
合成路线图解说明:

It is prepared by hydrolysis with ammonia in methanol of N-(3-acetylthio-2-methylpropanoyl)-L-proline (I). Compound (I) can be obtained in three different ways: 1) The reaction of L-proline tert-butyl ester (II) with 3-acetylthio-2-methyl-propanoic acid (III) by means of dicyclohexylcarbodiimide in CH2Cl2 gives N-(3-acetylthio-2-methylpropanoyl)-L-proline tert-butyl ester (IV), which is hydrolyzed with trifluoroacetic acid in anisole. 2) By condensation of L-proline (V) with 3-acetylthio-2-methylpropanoyl chloride (VI) (prepared from the corresponding acid (III) with SOCl2) by means of NaOH in water. 3) The condensation of L-proline (V) with methacryloyl chloride (VII) by means of NaHCO3 in water yields N-methacryloyl-L-proline (VIII), which is then treated with thiolacetic acid (A) and azobisisobutyronitrile. The acid (III) is obtained by addition of thiolacetic acid (IX) to methacrylic acid (X) at 100 C.

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