4-chlorobutyl 3-pyridinylmethyl sulfide; 3-[[(4-chlorobutyl)sulfanyl]methyl]pyridine -Drug Synthesis Database

【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 合成路线2

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.

参考文献中间体

合成目标

【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.

参考文献中间体

合成目标

【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	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