methyl (3R)-3-amino-3-(4-methoxyphenyl)propanoate -Drug Synthesis Database

【结构式】

【分子编号】59022

【品名】methyl (3R)-3-amino-3-(4-methoxyphenyl)propanoate

【CA登记号】

【分子式】C₁₁H₁₅NO₃

【分子量】209.24504

【元素组成】C 63.14% H 7.23% N 6.69% O 22.94%

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：(VII)

The Michael addition of the chiral amine (II) to methyl 4-(benzyloxy)cinnamate (I) in the presence of butyllithium produces diastereoselectively the amino ester (III) as the major isomer. After catalytic hydrogenolysis of the benzyl groups of (III), the resultant amino ester (IV) is converted to the N-Boc derivative (V) upon treatment with Boc2O. O-alkylation of phenol (V) with iodomethane in the presence of Cs2CO3 yields methyl ether (VI). The N-Boc group of (VI) is subsequently removed under acidic conditions to furnish (VII).

参考文献中间体

合成目标

【1】 Kopka, I.E.; Mumford, R.A.; Lin, L.S.; et al.; The discovery of acylated beta-amino acids as potent and orally bioavailable VLA-4 antagonists. Bioorg Med Chem Lett 2002, 12, 4, 611.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	59017	methyl (E)-3-[4-(benzyloxy)phenyl]-2-propenoate	C₁₇H₁₆O₃	详情	详情
(II)	47881	(1R)-N-benzyl-1-phenyl-1-ethanamine; N-benzyl-N-[(1R)-1-phenylethyl]amine	C₁₅H₁₇N	详情	详情
(III)	59018	methyl (3R)-3-[4-(benzyloxy)phenyl]-3-{benzyl[(1R)-1-phenylethyl]amino}propanoate	C₃₂H₃₃NO₃	详情	详情
(IV)	59019	methyl (3R)-3-amino-3-(4-hydroxyphenyl)propanoate	C₁₀H₁₃NO₃	详情	详情
(V)	59020	methyl (3R)-3-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propanoate	C₁₅H₂₁NO₅	详情	详情
(VI)	59021	methyl (3R)-3-[(tert-butoxycarbonyl)amino]-3-(4-methoxyphenyl)propanoate	C₁₆H₂₃NO₅	详情	详情
(VII)	59022	methyl (3R)-3-amino-3-(4-methoxyphenyl)propanoate	C₁₁H₁₅NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Condensation of 3,5-dichlorobenzenesulfonyl chloride (VIII) with (S)-azetidine-2-carboxylic acid (IX) under Schotten-Baumann conditions gives sulfonamide (X). This is subsequently coupled with aminoester (VII) by means of PyBOP to afford amide (XI). The methyl ester group of (XI) is finally hydrolyzed to the target carboxylic acid employing LiOH.

参考文献中间体

合成目标

【1】 Kopka, I.E.; Mumford, R.A.; Lin, L.S.; et al.; The discovery of acylated beta-amino acids as potent and orally bioavailable VLA-4 antagonists. Bioorg Med Chem Lett 2002, 12, 4, 611.
【2】 Hagmann, W.K.; Durette, P.L.; Mumford, R.A.; Kopka, I.E.; Mills, S.G.; MacCoss, M.; Magriotis, P.A. (Merck & Co., Inc.); Substd. beta-alanine derivs. as cell adhesion inhibitors. WO 0071572 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	59023	3,5-dichlorobenzenesulfonyl chloride		C₆H₃Cl₃O₂S	详情	详情
(IX)	26204	(2S)-2-azetidinecarboxylic acid; (S)-(-)-Azetidine carboxylic acid	2133-34-8	C₄H₇NO₂	详情	详情
(X)	59024	(2S)-1-[(3,5-dichlorophenyl)sulfonyl]-2-azetidinecarboxylic acid		C₁₀H₉Cl₂NO₄S	详情	详情
(XI)	59022	methyl (3R)-3-amino-3-(4-methoxyphenyl)propanoate		C₁₁H₁₅NO₃	详情	详情
(XII)	59025	methyl (3R)-3-[({(2S)-1-[(3,5-dichlorophenyl)sulfonyl]azetidinyl}carbonyl)amino]-3-(4-methoxyphenyl)propanoate		C₂₁H₂₂Cl₂N₂O₆S	详情	详情

Extended Information