(2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropionic acid -Drug Synthesis Database

【结构式】

【分子编号】20812

【品名】(2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropionic acid

【CA登记号】20887-95-0

【分子式】C₈H₁₅NO₄S

【分子量】221.27744

【元素组成】C 43.42% H 6.83% N 6.33% O 28.92% S 14.49%

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：(XIV)

2) The addition of tert-butoxycarbonyl)-L-cysteine (XIV) to 2-(2-nitroethenyl)thiophene (XV) by means of N-methylmorpholine in toluene gives S-[2-nitro-1-(2-thienyl)ethyl-N-(tert-butoxycarbonyl-L-cysteine (XVI), which is reduced with H2 over Pd/C in acetic acid yielding the corresponding amine (XVII). The cyclization of (XVII) by means of diphenyl phosphorazidate (DPN) and N-methylmorpholine in DMF affords (2RS,6R)-6-(tert-butoxycarbonylamino)-2-(2-thienyl)perhydro-1,4-thiazepine (XVIII), which by hydrolysis and fractional crystallization gives (2S,6R)-6-amino-2-(2-thienyl)perhydro-1,4-thiazepine (XIX). The condensation of (XIX) with ethyl 2(R)-(trifluoromethylsulfonyloxy)-4-phenylbutanoate (XX) by means of triethylamine in dichloromethane yields (2S,2R)-6-[1(S)-(ethoxycarbonyl)-3-phenylpropylamino]-2-(2-thienyl)- perhydro-1,4-thiazepin-5-one (XXI), which is condensed with tert-butyl bromoacetate (XXII) by means of NaH in DMF to give the precursor (XXIII). Finally, this compound is hydrolyzed with 4N-HCl-dioxane at room temperature.

参考文献中间体

合成目标

【1】 Yanagisawa, H.; Ishihara, S.; Ando, A.; Kanazaki, T.; Koike, H.; Tsujita, Y. (Sankyo Co., Ltd.); Perhydrothiazepine derivatives, their preparation and their therapeutical use. AU 8541058; EP 0161801; ES 8702388; ES 8801229; JP 85215678; JP 86267579 .
【2】 Ishihara, S.; Ando, A.; Miyamoto, S.; Kanazaki, T.; Hata, T.; Oizumi, K.; Matsushita, Y.; Koike, H.; Yanagisawa, H.; Iijima, Y.; Angiotensin-converting enzyme inhibitors: Perhydro-1,4-thiazepin-5-one derivatives. J Med Chem 1987, 30, 11, 1984.
【3】 Prous, J.; Castaner, J.; RS-5142. Drugs Fut 1989, 14, 4, 336.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	20812	(2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropionic acid	20887-95-0	C₈H₁₅NO₄S	详情	详情
(XV)	20813	2-[(Z)-2-nitroethenyl]thiophene		C₆H₅NO₂S	详情	详情
(XVI)	20814	(2R)-2-[(tert-butoxycarbonyl)amino]-3-[[2-nitro-1-(2-thienyl)ethyl]sulfanyl]propionic acid		C₁₄H₂₀N₂O₆S₂	详情	详情
(XVII)	20815	(2R)-3-[[2-amino-1-(2-thienyl)ethyl]sulfanyl]-2-[(tert-butoxycarbonyl)amino]propionic acid		C₁₄H₂₂N₂O₄S₂	详情	详情
(XVIII)	20816	tert-butyl (6R)-5-oxo-2-(2-thienyl)-1,4-thiazepan-6-ylcarbamate		C₁₄H₂₀N₂O₃S₂	详情	详情
(XIX)	20817	(2S,6R)-6-amino-2-(2-thienyl)-1,4-thiazepan-5-one	110221-26-6	C₉H₁₂N₂OS₂	详情	详情
(XX)	20818	ethyl (2R)-4-phenyl-2-[[(trifluoromethyl)sulfonyl]oxy]butanoate		C₁₃H₁₅F₃O₅S	详情	详情
(XXI)	20819	ethyl (2S)-2-[[(2S,6R)-5-oxo-2-(2-thienyl)-1,4-thiazepan-6-yl]amino]-4-phenylbutanoate		C₂₁H₂₆N₂O₃S₂	详情	详情
(XXII)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(XXIII)	20821	ethyl (2S)-2-[[(2S,6R)-4-[2-(tert-butoxy)-2-oxoethyl]-5-oxo-2-(2-thienyl)-1,4-thiazepan-6-yl]amino]-4-phenylbutanoate		C₂₇H₃₆N₂O₅S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The treatment of 4-(dimethylamino)benzyl alcohol (I) with concentrated HBr at 120 C in a sealed tube provided benzyl bromide (II). This was then condensed with N-Boc-L-cysteine (III) in the presence of N,N-diisopropyl ethylamine to furnish the benzyl thioether (IV). Subsequent cleavage of the Boc group of (IV) employing HCl in dioxan yielded the intermediate aminoacid (V).

参考文献中间体

合成目标

【1】 Miyake, Y.; Horiuchi, M.; Mita, S.; Tsuji, F.; Involvement of leukotriene B4 in murine dermatitis models. Biochem Pharmacol 1998, 55, 297.
【2】 Kawashima, Y.; Horiuchi, M. (Santen Pharmaceutical Co., Ltd.); Novel amino acid derivs. having N,N-dialkylaminophenyl group. EP 0870762; JP 1996301840; WO 9627585 .

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)	41579	[4-(dimethylamino)phenyl]methanol	1703-46-4	C₉H₁₃NO	详情	详情
(II)	41580	4-(bromomethyl)-N,N-dimethylaniline; N-[4-(bromomethyl)phenyl]-N,N-dimethylamine		C₉H₁₂BrN	详情	详情
(III)	20812	(2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropionic acid	20887-95-0	C₈H₁₅NO₄S	详情	详情
(IV)	41581	(2R)-2-[(tert-butoxycarbonyl)amino]-3-[[4-(dimethylamino)benzyl]sulfanyl]propionic acid		C₁₇H₂₆N₂O₄S	详情	详情
(V)	41582	(2R)-2-amino-3-[[4-(dimethylamino)benzyl]sulfanyl]propionic acid		C₁₂H₁₈N₂O₂S	详情	详情

Extended Information