3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]-1-propanol -Drug Synthesis Database

【结构式】

【分子编号】30240

【品名】3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]-1-propanol

【CA登记号】

【分子式】C₁₃H₁₆N₂O₂S

【分子量】264.34832

【元素组成】C 59.07% H 6.1% N 10.6% O 12.1% S 12.13%

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：(XIX)

Alternatively, the intermediate chiral hydroxy sulfoxide (XIX) was prepared by the following procedures. Alkylation of mercaptoimidazole (I) with 3-chloropropanol (XVII) gave thioether (XVIII). This was oxidized with cumene hydroperoxide and titanium tetraisopropoxide in the presence of either D-diethyl tartrate or (R)-mandelic acid as the chiral auxiliaries to provide, after recrystallization from methyl ethyl ketone, the optically pure sulfoxide (XIX). Subsequent treatment with methanesulfonyl chloride and triethylamine gave mesylate (XX), which was finally condensed with the sodium salt of 6-hydroxytetrahydroquinolinone (XXI) in DMSO at 60 C.

参考文献中间体

合成目标

【1】 Matsugi, M.; et al.; Practical asymmetric oxidation of 3-[1-(2-methylphenyl)imidazol-2-ylthio]propan-1-ol based on a titanium-mandelic acid complex. Tetrahedron Lett 1998, 39, 31, 5591.
【2】 Nishi, T.; Uno, T.; Shu, Y.; Tamura, K.; Okada, M. (Otsuka Pharmaceutical Co., Ltd.); Carbostyril derivs.. EP 0651747; JP 1995033765; US 5541198; WO 9426732 .

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)	30223	1-(2-methylphenyl)-1H-imidazol-2-ylhydrosulfide; 1-(2-methylphenyl)-1H-imidazole-2-thiol		C₁₀H₁₀N₂S	详情	详情
(XVII)	19490	3-chloro-1-propanol	627-30-5	C₃H₇ClO	详情	详情
(XVIII)	30239	3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfanyl]-1-propanol		C₁₃H₁₆N₂OS	详情	详情
(XIX)	30240	3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]-1-propanol		C₁₃H₁₆N₂O₂S	详情	详情
(XX)	30241	3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]propyl methanesulfonate		C₁₄H₁₈N₂O₄S₂	详情	详情
(XXI)	30242	sodium 2-oxo-1,2,3,4-tetrahydro-6-quinolinolate		C₉H₈NNaO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIX)

An alternative procedure for the chiral hydroxy sulfoxide (XIX) involved a lipase-catalyzed kinetic resolution. Transesterification of racemic hydroxy sulfoxide (XXII) with isopropenyl acetate (XXIII) catalyzed by lipase AL yielded the acetate ester of the required (S)-isomer (XXIV), along with the unreacted (R)-alcohol (XXV). Separation was achieved upon treatment with phthalic anhydride (XXVI) in the presence of DMAP and pyridine to produce the phthalic acid derivative (XXVII) of the unreacted alcohol, which could be separated from the desired acetate ester (XXIV) by means of selective extraction. The target enantiomerically pure (S)-hydroxy sulfoxide intermediate (XIX) was then obtained by methanolysis of the acetate ester (XXIV) with K2CO3, followed by two recrystallizations from EtOAc. The corresponding (R)-alcohol was recovered by NaOH hydrolysis of the phthalate ester (XXVII), and was completely racemized by treatment with aqueous HCl.

参考文献中间体

合成目标

【1】 Morita, S.; et al.; Synthesis of a key intermediate, (S)-2-[(3-hydroxypropyl)sulfinyl]-1-(o-tolyl)imidazole, for the antiplatelet aggregation inhibitor, OPC-29030 via lipase-catalyzed enantioselective transesterification. Tetrahedron Asymmetry 1997, 8, 22, 3707.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIX)	30240	3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]-1-propanol		C₁₃H₁₆N₂O₂S	详情	详情
(XXII)	30245	3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]-1-propanol		C₁₃H₁₆N₂O₂S	详情	详情
(XXIII)	21178	isopropenyl acetate	108-22-5	C₅H₈O₂	详情	详情
(XXIV)	30243	3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]propyl acetate		C₁₅H₁₈N₂O₃S	详情	详情
(XXV)	30246	3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]-1-propanol		C₁₃H₁₆N₂O₂S	详情	详情
(XXVI)	11900	2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride	85-44-9	C₈H₄O₃	详情	详情
(XXVII)	30244	2-[(3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfinyl]propoxy)carbonyl]benzoic acid		C₂₁H₂₀N₂O₅S	详情	详情

Extended Information