tert-butyl (2S)-2-amino-3-(2',6'-dimethoxy[1,1'-biphenyl]-4-yl)propanoate -Drug Synthesis Database

【结构式】

【分子编号】52095

【品名】tert-butyl (2S)-2-amino-3-(2',6'-dimethoxy[1,1'-biphenyl]-4-yl)propanoate

【CA登记号】

【分子式】C₂₁H₂₇NO₄

【分子量】357.44972

【元素组成】C 70.56% H 7.61% N 3.92% O 17.9%

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)

N-Boc-L-tyrosine tert-butyl ester (I) was converted to the aryl triflate (II) by means of trifluoromethanesulfonic anhydride and pyridine. Palladium-catalyzed coupling of triflate (II) with 2,6-dimethoxyphenylboronic acid (III) furnished the biphenyl compound (IV). The N-Boc protecting group of (IV) was then selectively removed by treatment with sulfuric acid in tert-butyl acetate, yielding amino ester (V).

参考文献中间体

合成目标

【1】 Yang, G.X.; Hagmann, W.K.; Doherty, G.; Chang, L.L.; Delaszlo, S.E. (Merck & Co., Inc.); Heterocycle amides as cell adhesion inhibitors. WO 0112183 .

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)	52092	tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propanoate		C₁₈H₂₇NO₅	详情	详情
(II)	52093	tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-[[(trifluoromethyl)sulfonyl]oxy]phenyl)propanoate		C₁₉H₂₆F₃NO₇S	详情	详情
(III)	32549	2,6-dimethoxyphenylboronic acid	23112-96-1	C₈H₁₁BO₄	详情	详情
(IV)	52094	tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(2',6'-dimethoxy[1,1'-biphenyl]-4-yl)propanoate		C₂₆H₃₅NO₆	详情	详情
(V)	52095	tert-butyl (2S)-2-amino-3-(2',6'-dimethoxy[1,1'-biphenyl]-4-yl)propanoate		C₂₁H₂₇NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Coupling of 2-tetrahydrofuroic acid (VI) with ortho-aminophenol (VII) by means of PyBOP gave the corresponding ortho-hydroxyanilide (VIII), which was cyclized to the benzoxazole (IX) in the presence of DEAD and triphenylphosphine. The lithium derivative of (IX) was acylated with methyl chloroformate to produce the carboxylate ester (X). Acid (XI), generated by basic hydrolysis of ester (X), was then coupled with amino ester (V) to afford amide (XII). The tert-butyl ester group of (XII) was finally cleaved to the title carboxylic acid by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Yang, G.X.; Hagmann, W.K.; Doherty, G.; Chang, L.L.; Delaszlo, S.E. (Merck & Co., Inc.); Heterocycle amides as cell adhesion inhibitors. WO 0112183 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	52095	tert-butyl (2S)-2-amino-3-(2',6'-dimethoxy[1,1'-biphenyl]-4-yl)propanoate		C₂₁H₂₇NO₄	详情	详情
(VI)	52096	Tetrahydrofuran-2-carboxylic Acid; 2-Tetrahydrofuroic acid	16874-33-2	C₅H₈O₃	详情	详情
(VII)	18663	o-aminophenol; 2-aminophenol	95-55-6	C₆H₇NO	详情	详情
(VIII)	52097	N-(2-hydroxyphenyl)tetrahydro-2-furancarboxamide		C₁₁H₁₃NO₃	详情	详情
(IX)	52098	2-tetrahydro-2-furanyl-1,3-benzoxazole		C₁₁H₁₁NO₂	详情	详情
(X)	52099	methyl 2-(1,3-benzoxazol-2-yl)tetrahydro-2-furancarboxylate		C₁₃H₁₃NO₄	详情	详情
(XI)	52100	2-(1,3-benzoxazol-2-yl)tetrahydro-2-furancarboxylic acid		C₁₂H₁₁NO₄	详情	详情
(XII)	52101	tert-butyl (2S)-2-([[2-(1,3-benzoxazol-2-yl)tetrahydro-2-furanyl]carbonyl]amino)-3-(2',6'-dimethoxy[1,1'-biphenyl]-4-yl)propanoate		C₃₃H₃₆N₂O₇	详情	详情

Extended Information