methyl (2S)-3-amino-2-[[(3-methylphenyl)sulfonyl]amino]propanoate -Drug Synthesis Database

【结构式】

【分子编号】28133

【品名】methyl (2S)-3-amino-2-[[(3-methylphenyl)sulfonyl]amino]propanoate

【CA登记号】

【分子式】C₁₁H₁₆N₂O₄S

【分子量】272.32512

【元素组成】C 48.52% H 5.92% N 10.29% O 23.5% S 11.77%

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)

Preparation of intermediate (IV) is illustrated in Scheme 25654801a: Methyl N3-Boc-(S)-2,3-diaminopropionate (I) was condensed with m-toluenesulfonyl chloride (II) to provide sulfonamide (III). The Boc group was then deprotected with HCl in dioxan to give amine (IV).

参考文献中间体

合成目标

【1】 Wityak, J.; Xue, C.-B.; Sielecki-Dzurdz, T.M.; Olson, R.E.; Degrado, W.F.; Cain, G.A. (DuPont Pharmaceuticals Co.); Novel isoxazoline and isoxazole fibrinogen receptor antagonists. EP 0730590; EP 0832076; JP 1997505590; JP 1999504651; US 5849736; WO 9514683; WO 9638426 .

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)	25095	methyl (2S)-2-amino-3-[(tert-butoxycarbonyl)amino]propanoate		C₉H₁₈N₂O₄	详情	详情
(II)	23316	3-methylbenzenesulfonyl chloride	1899-93-0	C₇H₇ClO₂S	详情	详情
(III)	28132	methyl (2S)-3-[(tert-butoxycarbonyl)amino]-2-[[(3-methylphenyl)sulfonyl]amino]propanoate		C₁₆H₂₄N₂O₆S	详情	详情
(IV)	28133	methyl (2S)-3-amino-2-[[(3-methylphenyl)sulfonyl]amino]propanoate		C₁₁H₁₆N₂O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Oxime (VI) was prepared from 4-cyanobenzaldehyde (V) upon treatment with hydroxylamine-HCl and pyridine. The nitrile oxide generated from oxime (VI) and NaOCl underwent a dipolar cycloaddition to methyl butenoate (VII) to produce the racemic isoxazoline (VIII). After conversion of the nitrile group of (VIII) to imidate (IX), reaction with methanolic ammonia yielded amidine (X), which was protected with Boc2O to give (XI). Hydrolysis of the methyl ester of (XI) with LiOH provided carboxylic acid (XII), which was coupled to amine (IV) using TBTU to afford amide (XIII) as a diasteromeric mixture. After Boc group removal by acidic treatment yielding (XIV), its methyl ester group was hydrolyzed with LiOH to afford the corresponding acid. The diastereomeric mixture of carboxylic acids was finally separated by preparative chiral HPLC.

参考文献中间体

合成目标

【1】 Wityak, J.; Xue, C.-B.; Sielecki-Dzurdz, T.M.; Olson, R.E.; Degrado, W.F.; Cain, G.A. (DuPont Pharmaceuticals Co.); Novel isoxazoline and isoxazole fibrinogen receptor antagonists. EP 0730590; EP 0832076; JP 1997505590; JP 1999504651; US 5849736; WO 9514683; WO 9638426 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	28133	methyl (2S)-3-amino-2-[[(3-methylphenyl)sulfonyl]amino]propanoate		C₁₁H₁₆N₂O₄S	详情	详情
(V)	17552	4-formylbenzonitrile; 4-Cyanobenzaldehyde	105-07-7	C₈H₅NO	详情	详情
(VI)	17553	4-[(hydroxyimino)methyl]benzonitrile		C₈H₆N₂O	详情	详情
(VII)	28134	methyl 3-butenoate		C₅H₈O₂	详情	详情
(VIII)	28135	methyl 2-[3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate		C₁₃H₁₂N₂O₃	详情	详情
(IX)	28136	methyl 2-(3-[4-[imino(methoxy)methyl]phenyl]-4,5-dihydro-5-isoxazolyl)acetate		C₁₄H₁₆N₂O₄	详情	详情
(X)	28137	methyl 2-(3-[4-[amino(imino)methyl]phenyl]-4,5-dihydro-5-isoxazolyl)acetate		C₁₃H₁₅N₃O₃	详情	详情
(XI)	28138	methyl 2-[3-(4-[amino[(tert-butoxycarbonyl)imino]methyl]phenyl)-4,5-dihydro-5-isoxazolyl]acetate		C₁₈H₂₃N₃O₅	详情	详情
(XII)	28139	2-[3-(4-[amino[(tert-butoxycarbonyl)imino]methyl]phenyl)-4,5-dihydro-5-isoxazolyl]acetic acid		C₁₇H₂₁N₃O₅	详情	详情
(XIII)	28140	methyl (2S)-3-[[2-(3-[4-[[(tert-butoxycarbonyl)amino](imino)methyl]phenyl]-4,5-dihydro-5-isoxazolyl)acetyl]amino]-2-[[(3-methylphenyl)sulfonyl]amino]propanoate		C₂₈H₃₅N₅O₈S	详情	详情
(XIV)	28141	methyl (2S)-3-[[2-(3-[4-[amino(imino)methyl]phenyl]-4,5-dihydro-5-isoxazolyl)acetyl]amino]-2-[[(3-methylphenyl)sulfonyl]amino]propanoate		C₂₃H₂₇N₅O₆S	详情	详情

Extended Information