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【结 构 式】

【分子编号】44409

【品名】4-chlorobutyl 3-pyridinylmethyl sulfide; 3-[[(4-chlorobutyl)sulfanyl]methyl]pyridine

【CA登记号】

【 分 子 式 】C10H14ClNS

【 分 子 量 】215.7466

【元素组成】C 55.67% H 6.54% Cl 16.43% N 6.49% S 14.86%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(V)

The reaction of 3-(chloromethyl)pyridine (I) with thiourea (II) in ethanol gives S-(3-pyridylmethyl)isothiourea (III), which is condensed with 4-chlorobutyl bromide (IV) by means of NaOH in dichloromethane to yield 3-(4-chlorobutylsulfanylmethyl)pyridine (V). The careful oxidation of (V) with MCPBA in dichloromethane affords the corresponding sulfoxide (VI), which is cyclized by means of potassium tert-butoxide in THF, providing a mixture of cis- and trans-2-(3-pyridyl)tetrahydrothiopyran S-oxide (VII + VIII). This mixture can be separated by conventional methods; however, when this mixture (VII + VIII), or either (VII) or (VIII) separately, are treated with NaNH2 and methyl isothiocyanate, only the target (1RS,2RS)-compound is obtained. Alternatively, the mixture (VII + VIII) or either (VII) or (VIII) can also be treated with potassium tert-butoxide, CS2 and methyl iodide to yield the (1RS,2RS)-dithioester (IX), which is finally converted into the target compound by reaction with methylamine.

1 Aloup, J.C.; Farge, D.; James, C.; Mondot, S.; Cavero, I.; 2-(3-PYRIDYL)-TETRAHYDROTHIOPYRAN-2-CARBOTHIOAMIDE DERIVATIVES AND ANALOGUES: A NOVEL FAMILY OF POTENT POTASSIUM CHANNEL OPENERS. Drugs Fut 1990, 15, 11, 1097.
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) 15793 3-(Chloromethyl)pyridine 3099-31-8 C6H6ClN 详情 详情
(II) 10180 Thiourea 62-56-6 CH4N2S 详情 详情
(III) 44408 3-([[amino(imino)methyl]sulfanyl]methyl)pyridine C7H9N3S 详情 详情
(IV) 16141 1-bromo-4-chlorobutane 6940-78-9 C4H8BrCl 详情 详情
(V) 44409 4-chlorobutyl 3-pyridinylmethyl sulfide; 3-[[(4-chlorobutyl)sulfanyl]methyl]pyridine C10H14ClNS 详情 详情
(VI) 44410 3-[[(4-chlorobutyl)sulfinyl]methyl]pyridine; 4-chlorobutyl 3-pyridinylmethyl sulfoxide C10H14ClNOS 详情 详情
(VII) 44412 (2R)-2-(3-pyridinyl)tetrahydro-1lambda(4)-thiopyran-1(2H)-one C10H13NOS 详情 详情
(VIII) 44411 (2R)-2-(3-pyridinyl)tetrahydro-1lambda(4)-thiopyran-1(2H)-one C10H13NOS 详情 详情
(IX) 44413 methyl (2S)-1-oxo-2-(3-pyridinyl)hexahydro-1lambda(4)-thiopyran-2-carbodithioate C12H15NOS3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(I)

The cyclization of 3-(4-chlorobutylsulfanylmethyl)pyridine (I) by means of n-BuLi in THF/HMPT gives 3-(tetrahydrothiopyran-2-yl)pyridine (II), which is treated with CS2, CH3I and KOtBu in the same solvent to yield the methyl carbodithioate (IV). The controlled oxidation of (IV) with MCPBA in dichloromethane affords the sulfoxide (IV), which is treated with methylamine in ethanol to provide a mixture of two racemic diastereomers that are separated by chromatography; however, the authors do not indicate the configuration of both racemates.

1 Aloup, J.-C.; Bouchaudon, J.; Farge, D.; James, C. (Aventis SA); Novel thioformamide derivs., their preparation and medicines containing them. EP 0097584 .
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) 44409 4-chlorobutyl 3-pyridinylmethyl sulfide; 3-[[(4-chlorobutyl)sulfanyl]methyl]pyridine C10H14ClNS 详情 详情
(II) 44414 3-tetrahydro-2H-thiopyran-2-ylpyridine C10H13NS 详情 详情
(III) 44415 methyl 2-(3-pyridinyl)tetrahydro-2H-thiopyran-2-carbodithioate C12H15NS3 详情 详情
(IV) 44416 methyl 1-oxo-2-(3-pyridinyl)hexahydro-1lambda(4)-thiopyran-2-carbodithioate C12H15NOS3 详情 详情
Extended Information