methyl N-[(4-chlorophenyl)sulfonyl]carbamate -Drug Synthesis Database

【结构式】

【分子编号】15813

【品名】methyl N-[(4-chlorophenyl)sulfonyl]carbamate

【CA登记号】

【分子式】C₈H₈ClNO₄S

【分子量】249.67456

【元素组成】C 38.49% H 3.23% Cl 14.2% N 5.61% O 25.63% S 12.84%

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：(XXXIV)

3) The cyclization of the previously described trans-4-(methanesulfonyloxy)-1-(3-pyridylmethyl)-L-prolinemethyl ester (XXI) with NaOH in acetonitrile gives the expected lactone (XXVIII), which by methanolysis with K2CO3 in methanol yields cis-4-hydroxy-1-(3-pyridylmethyl)-L-proline methyl ester (XXIX). The acylation of (XXIX) with 4-nitrophenylsulfonyl chloride (XXX) and triethylamine in dichloromethane affords the corresponding cis-sulfonyloxyproline derivative (XXXI), which is treated with the sodium salt of 4-chlorophenylsulfonamide (XXXII) in DMSO to give trans-4-(4-chlorophenylsulfonamido)-1-(3-pyridylmethyl)-L-proline methyl ester (XXV) already obtained. The reduction of (XXV) with NaBH4 in THF yields the corresponding hydroxymethyl derivative (XXXIII), which is oxidized with SO3/pyridine to the previously described aldehyde (XXVI). 4) The condensation of the previously described cis-4-hydroxyproline derivative (XXIX) with N-(4-chlorophenylsulfonyl)carbamic acid methyl ester (XXXIV) by means of triphenylphosphine and diethyl azodicarboxylate (DEAD) in THF gives (2S,4R)-trans-4-[4-chloro-N-(methoxycarbonyl)phenylsulfonamido]-1-(3-pyridylmethyl)pyrrolidine-2-carboxylic acid methyl ester (XXXV), which is reduced with NaBH4 to the trans-hydroxymethyl derivative (XXXIII), already described.

参考文献中间体

合成目标

【1】 Graul, A.; Castaner, J.; KDI-792. Drugs Fut 1996, 21, 12, 1224.
【2】 Kamijo, T.; Hokari, H.; Hirata, K.; Yanagi, T.; Oda, Y. (Kissei Pharmaceutical Co., Ltd.); Novel pyrrolidine derivs. JP 1995291965 .
【3】 Kamijo, T.; Hokari, H.; Hirata, K.; Yanagi, T.; Oda, Y. (Kissei Pharmaceutical Co., Ltd.); Novel pyrrolidine derivs. JP 1996012670 .
【4】 Kamijo, T.; Hokari, H.; Hirata, K.; Yanagi, T.; Oda, Y. (Kissei Pharmaceutical Co., Ltd.); Manufacturing method of (5Z)-6-[(2S,4R)-4-(4-chlorophenylsulfonylamino)-1-(3-pyridylmethyl)-2-pyrrolidinyl-5-hexenoic acid and its intermediates. JP 1995291966 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXI)	15800	methyl (2S,4R)-4-[(methylsulfonyl)oxy]-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate		C₁₃H₁₈N₂O₅S	详情	详情
(XXV)	15804	methyl (2S,4R)-4-[[(4-chlorophenyl)sulfonyl]amino]-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate		C₁₈H₂₀ClN₃O₄S	详情	详情
(XXVI)	15805	4-chloro-N-[(3R,5S)-5-formyl-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrol-3-yl]benzenesulfonamide		C₁₇H₁₈ClN₃O₃S	详情	详情
(XXVIII)	15807	(1S,4S)-5-(3-pyridinylmethyl)-2-oxa-5-azabicyclo[2.2.1]heptan-3-one		C₁₁H₁₂N₂O₂	详情	详情
(XXIX)	15808	methyl (2S,4S)-4-hydroxy-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate		C₁₂H₁₆N₂O₃	详情	详情
(XXX)	15809	4-nitrobenzenesulfonyl chloride	98-74-8	C₆H₄ClNO₄S	详情	详情
(XXXI)	15810	methyl (2S,4S)-4-[[(4-nitrophenyl)sulfonyl]oxy]-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate		C₁₈H₁₉N₃O₇S	详情	详情
(XXXII)	15811	4-Chlorobenzenesulfonamide sodium salt		C₆H₅ClNNaO₂S	详情	详情
(XXXIII)	15812	4-chloro-N-[(3R,5S)-5-(hydroxymethyl)-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrol-3-yl]benzenesulfonamide		C₁₇H₂₀ClN₃O₃S	详情	详情
(XXXIV)	15813	methyl N-[(4-chlorophenyl)sulfonyl]carbamate		C₈H₈ClNO₄S	详情	详情
(XXXV)	15814	methyl (2S,4R)-4-[[(4-chlorophenyl)sulfonyl](methoxycarbonyl)amino]-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate		C₂₀H₂₂ClN₃O₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Condensation of dihydropyrazole (I) with the sulfonyl carbamate (II) in the presence of pyridine gives rise to the 1-acyl dihydropyrazole (III). Subsequent chlorination of (III) using PCl5 in refluxing chlorobenzene affords the imidoyl chloride (IV). This is finally condensed with methylamine in CH2Cl2 to furnish the title compound.

参考文献中间体

合成目标

【1】 Kruse, C.G.; Tulp, M.T.M.; Lange, J.H.M.; Tipker, J.; Van Vliet, B.J. (Solvay Pharmaceuticals BV); 4,5-Dihydro-1H-pyrazole derivs. having CB 1-antagonistic activity. EP 1268435; US 2001053788; US 6476060; WO 0170700 .
【2】 Kruse, C.G.; Lange, J.H.M.; Tipker, J.; Hoogendoorn, J. (Solvay Pharmaceuticals BV); 4,5-Dihydro-1H-pyrazole derivs. having CB1-antagonistic activity. WO 0276949 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	58393	3-(4-chlorophenyl)-4-phenyl-4,5-dihydro-1H-pyrazole	C₁₅H₁₃ClN₂	详情	详情
(II)	15813	methyl N-[(4-chlorophenyl)sulfonyl]carbamate	C₈H₈ClNO₄S	详情	详情
(III)	58394	4-chloro-N-{[3-(4-chlorophenyl)-4-phenyl-4,5-dihydro-1H-pyrazol-1-yl]carbonyl}benzenesulfonamide	C₂₂H₁₇Cl₂N₃O₃S	详情	详情
(IV)	58395	3-(4-chlorophenyl)-N-[(4-chlorophenyl)sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboximidoyl chloride	C₂₂H₁₆Cl₃N₃O₂S	详情	详情

Extended Information