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

【结构式】

【分子编号】30239

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

【CA登记号】

【分子式】C₁₃H₁₆N₂OS

【分子量】248.34892

【元素组成】C 62.87% H 6.49% N 11.28% O 6.44% S 12.91%

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：(XVIII)

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：(V)

The cyclization of 2-methylphenyl isothiocyanate (I) with 2-aminoacetaldehyde dimethylacetal (II) in methanol gives the 1-(2-methylphenyl)imidazole-2-thiol (III), which is condensed with 3-bromopropanol (IV) by means of NaOH in refluxing water to yield the sulfide (V). The asymmetric oxidation of sulfide (V) with Ti(O-iPr)4, cumene hydroperoxide (CHP) and (R)-(-)-mandelic acid as chiral catalyst in dichloromethane affords the (S)-sulfinyl derivative (VI), which is treated with Ms-Cl to provide the expected mesylate (VII). Finally, this compound is condensed with the sodium salt of 6-hydroxy-1,2,3,4-tetrahydroquinolin-2one (VIII) to give the target compound.

参考文献中间体

合成目标

【1】 Matsugi, M.; et al.; Catalytic asymmetric oxidation of sulfide with titanium-mandelic acid complex: Practical synthesis of (S)-3-[1-(2-methylphenyl)imidazol-2-ylsulfinyl]propan-1-ol, the key intermediate of OPC-29030. Tetrahedron 2001, 57, 14, 2739.

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)	50207	6-isothiocyanato-1-methyl-1,3-cyclohexadiene; 2-methyl-2,4-cyclohexadien-1-yl isothiocyanate		C₈H₉NS	详情	详情
(II)	34158	aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine	22483-09-6	C₄H₁₁NO₂	详情	详情
(III)	30223	1-(2-methylphenyl)-1H-imidazol-2-ylhydrosulfide; 1-(2-methylphenyl)-1H-imidazole-2-thiol		C₁₀H₁₀N₂S	详情	详情
(IV)	12573	3-Bromo-1-propanol; 3-Bromopropanol	627-18-9	C₃H₇BrO	详情	详情
(V)	30239	3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfanyl]-1-propanol		C₁₃H₁₆N₂OS	详情	详情
(VI)	50208	(3-hydroxypropyl)[1-(2-methylphenyl)-1H-imidazol-2-yl]sulfoniumolate		C₁₃H₁₆N₂O₂S	详情	详情
(VII)	50209	[1-(2-methylphenyl)-1H-imidazol-2-yl][3-[(methylsulfonyl)oxy]propyl]sulfoniumolate		C₁₄H₁₈N₂O₄S₂	详情	详情
(VIII)	50210			C₉H₈NNaO₂	详情	详情

Extended Information