methyl (2S)-2-(acetylsulfanyl)propanoate -Drug Synthesis Database

【结构式】

【分子编号】16680

【品名】methyl (2S)-2-(acetylsulfanyl)propanoate

【CA登记号】

【分子式】C₆H₁₀O₃S

【分子量】162.2096

【元素组成】C 44.43% H 6.21% O 29.59% S 19.77%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(III)

Methylation of methyl (+)-lactate (I) followed by thioacetylation and acidic hydrolysis affords (-)-thiolactic acid (IV). Reaction of 3-pyridinecarboxyaldehyde (V) with methylamine in toluene under the azeotropic condition provides the imine (VI), which when condensed with (IV) affords (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one (VII). Treatment of (VII) with aqueous HCl/isopropanol results in the precipitation of SM-12502.

参考文献中间体

合成目标

【1】 Koike, H.; Natsume, Y.; Tojo, S.; Morooka, S.; SM-12502. Drugs Fut 1995, 20, 2, 153.

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)	11591	methyl (2R)-2-hydroxypropanoate	17392-83-5	C₄H₈O₃	详情	详情
(II)	16679	methyl (2R)-2-[(methylsulfonyl)oxy]propanoate		C₅H₁₀O₅S	详情	详情
(III)	16680	methyl (2S)-2-(acetylsulfanyl)propanoate		C₆H₁₀O₃S	详情	详情
(IV)	16681	(2S)-2-sulfanylpropionic acid		C₃H₆O₂S	详情	详情
(V)	12849	Nicotinaldehyde; 3-Pyridinecarboxaldehyde	500-22-1	C₆H₅NO	详情	详情
(VI)	16683	N-methyl-N-[(Z)-3-pyridinylmethylidene]amine; N-[(Z)-3-pyridinylmethylidene]methanamine		C₇H₈N₂	详情	详情
(VII)	16684	(2R,5S)-3,5-dimethyl-2-(3-pyridinyl)-1,3-thiazolan-4-one		C₁₀H₁₂N₂OS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

3) The condensation of 4-nitrobenzyl bromide (VI) with 4-amino-1,2,4-triazole (XII) in refluxing isopropanol gives 4-amino-1-(3-nitrobenzyl)-1,2,4-triazolium bromide (XIII), which is deaminated with NaNO2/HCl to afford 1-(4-nitrobenzyl)-1,2,4-triazole (VIII). The reduction of (VIII) yields amine (I), which by diazotation and reduction with Na2SO3 yields the corresponding hydrazine (IX). Finally, (IX) is cyclized with 4-(dimethylamino)butanal dimethylacetal (XIV) in acidic water.

参考文献中间体

合成目标

【1】 Castañer, J.; Mealy, N.; Rabassseda, X.; MK-0462. Drugs Fut 1995, 20, 7, 676.
【2】 Baker, R.; Pitt, K.G.; Matassa, V.G.; Storey, D.E.; Olive, C.; Street, L.J. (Merck Sharp & Dohme Ltd.); The sulphate salt of a substd. triazole, pharmaceutical compsns. thereof, and their use in therapy. EP 0573221; US 5527817; WO 9325547 .

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)	16680	methyl (2S)-2-(acetylsulfanyl)propanoate		C₆H₁₀O₃S	详情	详情
(VI)	16866	1-(Bromomethyl)-4-nitrobenzene; para-Nitrobenzyl bromide	100-11-8	C₇H₆BrNO₂	详情	详情
(VIII)	16868	1-(4-nitrobenzyl)-1H-1,2,4-triazole		C₉H₈N₄O₂	详情	详情
(XI)	16869	1-(4-hydrazinobenzyl)-1H-1,2,4-triazole		C₉H₁₁N₅	详情	详情
(XII)	16106	4H-1,2,4-triazol-4-amine; 4-Amino-4H-1,2,4-triazole; 4H-1,2,4-triazol-4-ylamine; 4-Amino-1,2,4-triazole	584-13-4	C₂H₄N₄	详情	详情
(XIII)	16873	4-amino-1-(4-nitrobenzyl)-1H-1,2,4-triazol-4-ium bromide	6085-99-0	C₉H₁₀BrN₅O₂	详情	详情
(XIV)	16874	N-(4,4-dimethoxybutyl)-N,N-diethylamine; N,N-diethyl-4,4-dimethoxy-1-butanamine		C₁₀H₂₃NO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Methyl (S)-lactate (I) was converted to chloride (II) by treatment with SOCl2. Subsequent displacement in (II) by cesium thioacetate produced thioester (III). Reduction of the ester group of (III) with concomitant thioester cleavage by means of LiAlH4 in cold THF furnished mercaptoalcohol (IV).

参考文献中间体

合成目标

【1】 Friesen, R.W.; Deschênes, D.; Gordon, R.; Brideau, C.; Riendau, D.; Savoie, C.; Dubé, D.; Girard, Y.; Fortin, R.; Chan, C.-C.; 2-Heterosubstituted-3-(4-methylsulfonyl)phenyl-5-trifluromethyl pyridines as selective and orally active cyclooxygenase-2 inhibitors. Bioorg Med Chem Lett 1999, 9, 12, 1715.

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)	17075	propionic acid, 2-hydroxy-, methyl ester, (S)-; methyl (2S)-2-hydroxypropanoate	27871-49-4	C₄H₈O₃	详情	详情
(II)	35742	methyl (2S)-2-chloropropanoate		C₄H₇ClO₂	详情	详情
(III)	16680	methyl (2S)-2-(acetylsulfanyl)propanoate		C₆H₁₀O₃S	详情	详情
(IV)	35743	(2S)-2-sulfanyl-1-propanol		C₃H₈OS	详情	详情

Extended Information