1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene -Drug Synthesis Database

【结构式】

【分子编号】43201

【品名】1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene

【CA登记号】

【分子式】C₁₀H₁₀ClNS

【分子量】211.71484

【元素组成】C 56.73% H 4.76% Cl 16.75% N 6.62% S 15.15%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The cyclization of 2-(2,4-dichloro-5-fluorobenzoyl)acetic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III), which is oxidized with MCPBA in dichloromethane, yielding the sulfinyl derivative (IV). The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazoloquinoline (V), which is finally condensed with piperazine in pyridine to furnish the target compound.

参考文献中间体

合成目标

【1】 Mohamadi, F.; Spees, M.M.; Grindey, G.B.; Antineoplastic bicyclic sulfonylureas. Bioorg Med Chem Lett 1992, 3, 987-992.
【2】 Chu, D.T.W.; Isothiazoloquinolones: Antibacterial and antineoplastic agents. Drugs Fut 1992, 17, 12, 1101.
【3】 Ehlhardt, W.J.; Woodland, J.M.; Worzalla, J.F.; Bewley, J.R.; Grindey, G.B.; Todd, G.C.; Toth, J.E.; Howbert, J.J.; Comparison of metabolism and toxicity to the structure of the anticancer agent sulofenur and related sulfonylureas. Chem Res Toxicol 1992, 5, 5, 667.

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)	22096	ethyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate		C₁₁H₉Cl₂FO₃	详情	详情
(II)	43201	1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene		C₁₀H₁₀ClNS	详情	详情
(III)	43208	ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-3-quinolinecarboxylate		C₂₁H₁₇ClFNO₃S	详情	详情
(IV)	43209	ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfinyl)-1,4-dihydro-3-quinolinecarboxylate		C₂₁H₁₇ClFNO₄S	详情	详情
(V)	43210	7-chloro-9-cyclopropyl-6-fluoroisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione		C₁₃H₈ClFN₂O₂S	详情	详情
(VI)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The cyclization of 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropionic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid ethyl ester (III), which is oxidized with MCPBA in dichloromethane, yielding the sulfinyl derivative (IV). The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazolonaphthyridine (V), which is finally condensed with piperazine in pyridine to furnish the target compound.

参考文献中间体

合成目标

【1】 Aquilar-Bryan, L.; Bryan, J.; Boyd, A.E. III; et al.; Sulfonylurea signal transduction. Recent Prog Horm Res 1991, 47, 299-317.
【2】 Chu, D.T.W.; Isothiazoloquinolones: Antibacterial and antineoplastic agents. Drugs Fut 1992, 17, 12, 1101.

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)	15228	ethyl 3-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-oxopropanoate		C₁₀H₈Cl₂FNO₃	详情	详情
(II)	43201	1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene		C₁₀H₁₀ClNS	详情	详情
(III)	43205	ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro[1,8]naphthyridine-3-carboxylate		C₂₀H₁₆ClFN₂O₃S	详情	详情
(IV)	42306	methyl 4-[5-(1,5-diisopropyl-1H-pyrazol-3-yl)-1H-pyrrol-2-yl]benzoate		C₂₁H₂₅N₃O₂	详情	详情
(V)	43027	tert-butyl (1S)-1-isobutyl-3-methyl-2-oxo-3-butenylcarbamate		C₁₄H₂₅NO₃	详情	详情
(VI)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The cyclization of 2-(2,4-dichloro-3,5-difluorobenzoyl)acetic acid ethyl ester (I) with S-phenyl(cyclopropylimino)chlorothioformate (II) by means of NaH in DMF gives 7-chloro-1-cyclopropyl-6,8-difluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III), which is oxidized with MCPBA in dichloromethane, yielding the sulfinyl derivative (IV). The cyclization of (IV) with NaSH and hydroxylamine-O-sulfonic acid in THF affords the isothiazoloquinoline (V), which is finally condensed with piperazine in pyridine to furnish the target compound.

参考文献中间体

合成目标

【1】 Aquilar-Bryan, L.; Bryan, J.; Boyd, A.E. III; et al.; Sulfonylurea signal transduction. Recent Prog Horm Res 1991, 47, 299-317.
【2】 Chu, D.T.W.; Isothiazoloquinolones: Antibacterial and antineoplastic agents. Drugs Fut 1992, 17, 12, 1101.

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)	43200	ethyl 3-(2,4-dichloro-3,5-difluorophenyl)-3-oxopropanoate		C₁₁H₈Cl₂F₂O₃	详情	详情
(II)	43201	1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene		C₁₀H₁₀ClNS	详情	详情
(III)	43202	ethyl 7-chloro-1-cyclopropyl-6,8-difluoro-4-oxo-2-(phenylsulfanyl)-1,4-dihydro-3-quinolinecarboxylate		C₂₁H₁₆ClF₂NO₃S	详情	详情
(IV)	43203	ethyl 7-chloro-1-cyclopropyl-6,8-difluoro-4-oxo-2-(phenylsulfinyl)-1,4-dihydro-3-quinolinecarboxylate		C₂₁H₁₆ClF₂NO₄S	详情	详情
(V)	43204	7-chloro-9-cyclopropyl-6,8-difluoroisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione		C₁₃H₇ClF₂N₂O₂S	详情	详情
(VI)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情

Extended Information