ethyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate -Drug Synthesis Database

【结构式】

【分子编号】26615

【品名】ethyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate

【CA登记号】

【分子式】C₁₃H₁₈N₂O₄

【分子量】266.297

【元素组成】C 58.63% H 6.81% N 10.52% O 24.03%

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：(V)

The reaction of N-(benzyloxycarbonyl)-L-asparagine (I) with bis(trifluoroacetyl)iodobenzene (BTI) in DMF/water gives 3-amino-2(S)-(benzyloxycarbonylamino)propionic acid (II), wehich is protected at the amino group with tert-butoxycarbonyl anhydride yielding carbamate (III). The esterification of (III) with ethanol WSC and DMAP affords the expected ethyl ester (IV), which is selectively deprotected with methanesulfonic acid in acetonitrile providing 3-amino-2-(benzyloxycarbonylamino)propionic acid ethyl ester (V). The condensation of (V) with N-(tert-butoxycarbonyl)-beta-alanine (VI) by means of HOBT, WSC and triethylamine in DMF gives the protected propionamidopropionic ester (VII), which is selectively deprotected by hydrogenation with H2 over Pd/C in ethanol/ethyl acetate giving the 2-aminopropionic ester (VIII). The condensation of (VIII) with 4-ethylbenzenesulfonyl chloride (IX) by means of triethylamine in dichloromethane yields the sulfonamide (X), which is deprotected with methanesulfonic acid as before afording intermediate (XI) with a free amino group, which is condensed with 4-(tert-butoxycarbonylamino)benzoic acid (XII) by means of HOBT and WSC in DMF providing the fully protected target compound (XIII).

参考文献中间体

合成目标

【1】 Ikeda, Y.; Ueki, Y.; Kishimoto, H.; Nishihara, T.; Kamikawa, Y. (Sumitomo Pharmaceuticals Co., Ltd.); 2,3-Diaminopropionic acid deriv.. US 5707994; US 6048854; WO 9511228 .

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)	14529	(2S)-4-amino-2-[[(benzyloxy)carbonyl]amino]-4-oxobutyric acid	2304-96-3	C₁₂H₁₄N₂O₅	详情	详情
(II)	18008	(2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propionic acid; N(alpha)-Z-L-2,3-diaminopropionic acid	35761-26-3	C₁₁H₁₄N₂O₄	详情	详情
(III)	26613	(2S)-2-[[(benzyloxy)carbonyl]amino]-3-[(tert-butoxycarbonyl)amino]propionic acid		C₁₆H₂₂N₂O₆	详情	详情
(IV)	26614	ethyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[(tert-butoxycarbonyl)amino]propanoate		C₁₈H₂₆N₂O₆	详情	详情
(V)	26615	ethyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate		C₁₃H₁₈N₂O₄	详情	详情
(VI)	26616	N-(tert-butoxycarbonyl)-beta-alanine	3303-84-2	C₈H₁₅NO₄	详情	详情
(VII)	26617	ethyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-([3-[(tert-butoxycarbonyl)amino]propanoyl]amino)propanoate		C₂₁H₃₁N₃O₇	详情	详情
(VIII)	26618	ethyl (2S)-2-amino-3-([3-[(tert-butoxycarbonyl)amino]propanoyl]amino)propanoate		C₁₃H₂₅N₃O₅	详情	详情
(IX)	26619	4-ethylbenzenesulfonyl chloride	16712-69-9	C₈H₉ClO₂S	详情	详情
(X)	26620	ethyl (2S)-3-([3-[(tert-butoxycarbonyl)amino]propanoyl]amino)-2-[[(4-ethylphenyl)sulfonyl]amino]propanoate		C₂₁H₃₃N₃O₇S	详情	详情
(XI)	26621	ethyl (2S)-3-[(3-aminopropanoyl)amino]-2-[[(4-ethylphenyl)sulfonyl]amino]propanoate		C₁₆H₂₅N₃O₅S	详情	详情
(XII)	26622	4-[[(tert-butoxycarbonyl)amino](imino)methyl]benzoic acid		C₁₃H₁₆N₂O₄	详情	详情
(XIII)	26623	ethyl (2S)-3-[[3-([4-[[(tert-butoxycarbonyl)amino](imino)methyl]benzoyl]amino)propanoyl]amino]-2-[[(4-ethylphenyl)sulfonyl]amino]propanoate		C₂₉H₃₉N₅O₈S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

After activation of acid (IX) as the mixed anhydride with isobutyl chloroformate, coupling with the mono-protected diaminopropionate (X) leads to amide (XI). Subsequent removal of the N-carbobenzoxy group by catalytic hydrogenolysis gives amino ester (XII). This is then acylated by 2-naphthalenesulfonyl chloride (XIII), yielding sulfonamide (XIV).

参考文献中间体

合成目标

【1】 Lesur, B.; Henry, M.; Yue, C.; Giboulot, T. (Laboratoires L. Lafon); Bispiperidines as antithrombotic agents. EP 1098878; FR 2781223; JP 2002520393; US 6333338; WO 0003986 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	63026	2-[(4-[1-(tert-butoxycarbonyl)-4-piperidinyl]-2-{2-[1-(tert-butoxycarbonyl)-4-piperidinyl]ethyl}butanoyl)amino]acetic acid		C₂₈H₄₉N₃O₇	详情	详情
(X)	26615	ethyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate		C₁₃H₁₈N₂O₄	详情	详情
(XI)	63027	tert-butyl 4-[(10S)-3-{2-[1-(tert-butoxycarbonyl)-4-piperidinyl]ethyl}-10-(ethoxycarbonyl)-4,7,12-trioxo-14-phenyl-13-oxa-5,8,11-triazatetradec-1-yl]-1-piperidinecarboxylate		C₄₁H₆₅N₅O₁₀	详情	详情
(XII)	63028	tert-butyl 4-{3-{[(2-{[(2S)-2-amino-3-ethoxy-3-oxopropyl]amino}-2-oxoethyl)amino]carbonyl}-5-[1-(tert-butoxycarbonyl)-4-piperidinyl]pentyl}-1-piperidinecarboxylate		C₃₃H₅₉N₅O₈	详情	详情
(XIII)	27989	2-naphthalenesulfonyl chloride	93-11-8	C₁₀H₇ClO₂S	详情	详情
(XIV)	63029	tert-butyl 4-[5-[1-(tert-butoxycarbonyl)-4-piperidinyl]-3-({[2-({(2S)-3-ethoxy-2-[(2-naphthylsulfonyl)amino]-3-oxopropyl}amino)-2-oxoethyl]amino}carbonyl)pentyl]-1-piperidinecarboxylate		C₄₃H₆₅N₅O₁₀S	详情	详情

Extended Information