Lemildipine, NB-818, NPK-1886, -Drug Synthesis Database

【结构式】

【药物名称】Lemildipine, NB-818, NPK-1886

【化学名称】(±)-2-(Aminocarbonyloxymethyl)-4-(2,3-dichlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 5-methyl 3-(1-methylethyl) ester
　　　　　　(±)-2-(Carbamoyloxymethyl)-4-(2,3-dichlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid 3-isopropyl 5-methyl ester

【CA登记号】125729-29-5, 94739-29-4 (undefined stereoch.)

【分子式】C₂₀H₂₂Cl₂N₂O₆

【分子量】457.31414

【开发单位】Banyu (Originator), Kowa (Licensee)

【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Calcium Channel Blockers

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

1) By cyclization of methyl 2-(2,3-dichlorobenzylidene)acetoacetate (I) with isopropyl 3-amino-4-(carbamoyloxy)crotonate (II).

参考文献中间体

【1】 Migano, T. et al. (Banyu Pharmaceutical Co., Ltd.); 2-N-Substd. or unsubstd.-carbamoyloxy-alkyl-1, 4-dihydropyridine-3,5-dicarboxylic acid symmetrical or asymmetrical diester deriv. and its preparation. JP 1984152373 .
【2】 Prous, J.; Castaner, J.; NB-818. Drugs Fut 1989, 14, 4, 331.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	20790	Methyl (Z)-2,3-dichlorobenzyldeneacetoacetate; Methyl (Z)-2-acetyl-3-(2,3-dichlorophenyl)-2-propenoate	74073-22-6	C₁₂H₁₀Cl₂O₃	详情	详情
(II)	20791	isopropyl (E)-3-amino-4-[(aminocarbonyl)oxy]-2-butenoate		C₈H₁₄N₂O₄	详情	详情

合成路线2

2) By cyclization of (I) with isopropyl 4-(carbamoyloxy)-2-butynoate (III) and ammonium acetate (IV).

参考文献中间体

【1】 Migano, T. et al. (Banyu Pharmaceutical Co., Ltd.); 2-N-Substd. or unsubstd.-carbamoyloxy-alkyl-1, 4-dihydropyridine-3,5-dicarboxylic acid symmetrical or asymmetrical diester deriv. and its preparation. JP 1984152373 .
【2】 Prous, J.; Castaner, J.; NB-818. Drugs Fut 1989, 14, 4, 331.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	20790	Methyl (Z)-2,3-dichlorobenzyldeneacetoacetate; Methyl (Z)-2-acetyl-3-(2,3-dichlorophenyl)-2-propenoate	74073-22-6	C₁₂H₁₀Cl₂O₃	详情	详情
(III)	20792	Acetylenedicarboxylic acid isopropyl ester carbamoyl anhydride		C₈H₉NO₅	详情	详情

合成路线3

By cyclization of (II) with 2,3-dichlorobenzaldehyde (V) and methyl acetoacetate (VI).

参考文献中间体

【1】 Migano, T. et al. (Banyu Pharmaceutical Co., Ltd.); 2-N-Substd. or unsubstd.-carbamoyloxy-alkyl-1, 4-dihydropyridine-3,5-dicarboxylic acid symmetrical or asymmetrical diester deriv. and its preparation. JP 1984152373 .
【2】 Prous, J.; Castaner, J.; NB-818. Drugs Fut 1989, 14, 4, 331.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	20791	isopropyl (E)-3-amino-4-[(aminocarbonyl)oxy]-2-butenoate		C₈H₁₄N₂O₄	详情	详情
(V)	14742	2,3-dichlorobenzaldehyde	6334-18-5	C₇H₄Cl₂O	详情	详情
(VI)	20794	methyl 2-oxobutanoate		C₅H₈O₃	详情	详情

合成路线4

By esterification of 3-isopropyl 5-methyl 4-(2,3-dichlorophenyl)-2-hydroxymethyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate (VII) with chlorosulfonyl isocyanate.

参考文献中间体

【1】 Miyano, T.; Suzuki, K. (Banyu Pharmaceutical Co., Ltd.); A novel method for producing carbamoyloxyalkyl-1, 4-dihydropyridine deriv.. JP 1985139671 .
【2】 Prous, J.; Castaner, J.; NB-818. Drugs Fut 1989, 14, 4, 331.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	20795	3-isopropyl 5-methyl 4-(2,3-dichlorophenyl)-2-(hydroxymethyl)-6-methyl-1,4-dihydro-3,5-pyridinedicarboxylate		C₁₉H₂₁Cl₂NO₅	详情	详情

Extended Information