tert-butyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropanoate -Drug Synthesis Database

【结构式】

【分子编号】42195

【品名】tert-butyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropanoate

【CA登记号】

【分子式】C₁₂H₂₃NO₄S

【分子量】277.38496

【元素组成】C 51.96% H 8.36% N 5.05% O 23.07% S 11.56%

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：(I)

Alkylation of N-Boc-L-cysteine tert-butyl ester (I) with the chiral tosylate (II) gave thioether (III). The N-benzyloxycarbonyl protecting group of (III) was then cleaved by transfer hydrogenolysis using ammonium formate in the presence of Pearlman's catalyst to afford amine (IV). Condensation of this amine with the thioacetimidate (V) gave rise to amidine (VI). The N-Boc and tert-butyl ester protecting groups of (VI) were finally removed by treatment with a solution of HCl in dioxan.

参考文献中间体

合成目标

【1】 Young, R.J.; et al.; Inhibition of inducible nitric oxide synthase by acetamidine derivatives of branched hetero-substituted lysine analogs. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 250.
【2】 Beswick, P.J.; Young, R.J.; Kleanthous, S. (Glaxo Group Ltd.); Nitric oxide synthase inhibitors. EP 1084104; WO 9962875 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	42195	tert-butyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropanoate	C₁₂H₂₃NO₄S	详情	详情
(II)	49913	(1S)-2-[[(benzyloxy)carbonyl]amino]-1-methylethyl 4-methylbenzenesulfonate	C₁₈H₂₁NO₅S	详情	详情
(III)	49914	tert-butyl (2R)-3-[((1R)-2-[[(benzyloxy)carbonyl]amino]-1-methylethyl)sulfanyl]-2-[(tert-butoxycarbonyl)amino]propanoate	C₂₃H₃₆N₂O₆S	详情	详情
(IV)	49915	tert-butyl (2R)-3-[[(1R)-2-amino-1-methylethyl]sulfanyl]-2-[(tert-butoxycarbonyl)amino]propanoate	C₁₅H₃₀N₂O₄S	详情	详情
(V)	42175	1-naphthylmethyl ethanimidothioate	C₁₃H₁₃NS	详情	详情
(VI)	49916	tert-butyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-[[(1R)-2-(ethanimidoylamino)-1-methylethyl]sulfanyl]propanoate	C₁₇H₃₃N₃O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

In a related procedure, N-Boc-L-cysteine tert-butyl ester (X) was prepared by reduction of N-Boc-cystine tert-butyl ester (IX) with dithiothreitol (DTT). Alkylation of thiol (X) with tosylate (II) afforded thioether (XI). After oxidation of (XI) to sulfone (XII), transfer hydrogenolysis using ammonium formate and palladium hydroxide on carbon removed the benzyloxycarbonyl group to furnish amine (XIII). This was converted to amidine (XIV) by treatment with thioacetimidate (VII). Finally, deprotection of the Boc group and the tert-butyl ester of (XIV) by means of HCl in dioxan afforded the title compound.

参考文献中间体

合成目标

【1】 Young, R.J.; et al.; Inhibition of inducible nitric oxide synthase by acetamidine derivatives of hetero-substituted lysine and homolysine. Bioorg Med Chem Lett 2000, 10, 6, 597.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(II)	42170	2-[[(benzyloxy)carbonyl]amino]ethyl 4-methylbenzenesulfonate	C₁₇H₁₉NO₅S	详情	详情
(VII)	42175	1-naphthylmethyl ethanimidothioate	C₁₃H₁₃NS	详情	详情
(IX)	42194	di(tert-butyl) (6R,11R)-2,2,15,15-tetramethyl-4,13-dioxo-3,14-dioxa-8,9-dithia-5,12-diazahexadecane-6,11-dicarboxylate	C₂₄H₄₄N₂O₈S₂	详情	详情
(X)	42195	tert-butyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropanoate	C₁₂H₂₃NO₄S	详情	详情
(XI)	42196	tert-butyl (2R)-3-[(2-[[(benzyloxy)carbonyl]amino]ethyl)sulfanyl]-2-[(tert-butoxycarbonyl)amino]propanoate	C₂₂H₃₄N₂O₆S	详情	详情
(XII)	42197	tert-butyl (2R)-3-[(2-[[(benzyloxy)carbonyl]amino]ethyl)sulfonyl]-2-[(tert-butoxycarbonyl)amino]propanoate	C₂₂H₃₄N₂O₈S	详情	详情
(XIII)	42198	tert-butyl (2R)-3-[(2-aminoethyl)sulfonyl]-2-[(tert-butoxycarbonyl)amino]propanoate	C₁₄H₂₈N₂O₆S	详情	详情
(XIV)	42199	tert-butyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-[[2-(ethanimidoylamino)ethyl]sulfonyl]propanoate	C₁₆H₃₁N₃O₆S	详情	详情

Extended Information