methyl (8S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】27316

【品名】methyl (8S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate

【CA登记号】

【分子式】C₈H₁₃NO₂S₂

【分子量】219.32876

【元素组成】C 43.81% H 5.97% N 6.39% O 14.59% S 29.24%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IV)

The cyclization of 1-benzyloxycarbonyl-4-oxoproline methyl ester (I) with ethanedithiol (II) by means of p-toluenesulfonic acid in refluxing acetic acid gives methyl 7-benzyloxycarbonyl-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate (III), which is deprotected with 20% HBr to give methyl 1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate (IV). The condensation of (IV) with N-benzyloxycarbonyl alanine N-hydroxysuccinimide ester (V) affords the corresponding dipeptide methyl ester (VI), which is hydrolyzed with NaOH to the free acid (VII), and deprotected with 20% HBr as before to 7-alanyl-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid (VIII). Finally, this compound is condensed with ethyl 2-oxo-4-phenylbutyrate (IX) by means of sodium cyanoborohydride in methanol.

参考文献中间体

合成目标

【1】 Smith, E.M.; Neustadt, B.R.; Gold, E.H. (Schering Corp.); 7-Carboxyalkylaminoacyl-1,4-dithia-7-azaspiro[4.4]-nonane-8-carboxylic acids. JP 1989163197; US 4470972 .
【2】 Prous, J.; Castaner, J.; Spirapril. Drugs Fut 1987, 12, 9, 860.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	27314	benzyl hydrogen sulfate		C₇H₈O₄S	详情	详情
(I)	27312	1-benzyl 2-methyl (2R)-4-oxo-1,2-cyclopentanedicarboxylate		C₁₅H₁₆O₅	详情	详情
(II)	27313	1,2-ethanedithiol	540-63-6	C₂H₆S₂	详情	详情
(III)	27315	7-benzyl 8-methyl (8R)-1,4-dithiaspiro[4.4]nonane-7,8-dicarboxylate		C₁₇H₂₀O₄S₂	详情	详情
(IV)	27316	methyl (8S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate		C₈H₁₃NO₂S₂	详情	详情
(V)	27317	benzyl (1S)-2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-1-methyl-2-oxoethylcarbamate		C₁₅H₁₆N₂O₆	详情	详情
(VI)	27318	methyl (8S)-7-((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate		C₁₉H₂₄N₂O₅S₂	详情	详情
(VII)	27319	(8S)-7-((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid		C₁₈H₂₂N₂O₅S₂	详情	详情
(VIII)	27320	(8S)-7-[(2S)-2-aminopropanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid		C₁₀H₁₆N₂O₃S₂	详情	详情
(IX)	20896	Ethyl 2-oxo-4-phenylbutanoate; 2-Oxo-4-phenylbutyric acid ethyl ester	64920-29-2	C₁₂H₁₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of (IX) with alanine benzyl ester (X) with sodium cyanoboohydride as before gives N-[1-(ethoxycarbonyl)-3-phenylpropyl]alanine benzyl ester (XI), which is submitted to fractional crystallization with maleic acid yielding N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine benzyl ester (XII), which is debenzylated by hydrogenation with H2 over Pd/C in ethanol yielding the free acid (XIII). Finally, this compound is condensed with spirane (IV) through the N-hydroxysuccinimide ester, in the usual way.

参考文献中间体

合成目标

【1】 Smith, E.M.; Neustadt, B.R.; Gold, E.H. (Schering Corp.); 7-Carboxyalkylaminoacyl-1,4-dithia-7-azaspiro[4.4]-nonane-8-carboxylic acids. JP 1989163197; US 4470972 .
【2】 Prous, J.; Castaner, J.; Spirapril. Drugs Fut 1987, 12, 9, 860.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	23808	Fumaric acid; (E)-2-butenedioic acid	110-17-8	C₄H₄O₄	详情	详情
(IV)	27316	methyl (8S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate		C₈H₁₃NO₂S₂	详情	详情
(IX)	20896	Ethyl 2-oxo-4-phenylbutanoate; 2-Oxo-4-phenylbutyric acid ethyl ester	64920-29-2	C₁₂H₁₄O₃	详情	详情
(X)	10143	benzyl (2S)-2-aminopropanoate		C₁₀H₁₃NO₂	详情	详情
(XI)	27321	ethyl 2-[[(1S)-2-(benzyloxy)-1-methyl-2-oxoethyl]amino]-4-phenylbutanoate		C₂₂H₂₇NO₄	详情	详情
(XII)	15665	ethyl (2S)-2-[[(1S)-2-(benzyloxy)-1-methyl-2-oxoethyl]amino]-4-phenylbutanoate		C₂₂H₂₇NO₄	详情	详情
(XIII)	11360	(2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]propionic acid; (S)-N-(1-Ethoxycarbonyl-3-phenylpropyl)-(S)-alanine	82717-96-2	C₁₅H₂₁NO₄	详情	详情

Extended Information