1,2-dichloro-3-isocyanatobenzene -Drug Synthesis Database

【结构式】

【分子编号】28667

【品名】1,2-dichloro-3-isocyanatobenzene

【CA登记号】41195-90-8

【分子式】C₇H₃Cl₂NO

【分子量】188.01236

【元素组成】C 44.72% H 1.61% Cl 37.71% N 7.45% O 8.51%

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：(VI)

The sulfonation of 3-aminobenzonitrile (I) with benzenesulfonyl chloride (II) by means of triethylamine in dichloromethane gives the sulfonamide (III), which is nitrated with HNO3 in acetic anhydride yielding 4-nitro-3-(phenyl sulfonamido)benzonitrile (IV). The reduction of (IV) with SnCl2 in hot ethanol affords the corresponding 4-amino derivative (V), which is finally condensed with 2,3-dichlorophenyl isocyanate (VI) in hot DMF.

参考文献中间体

合成目标

【1】 Widdowson, K.L.; Veber, D.F.; Jurewicz, A.J.; Rutledge, M.C. Jr.; Hertzberg, R.P. (SmithKline Beecham plc); IL-8 receptor antagonists. EP 0809492; JP 1999503110; US 5780483; WO 9625157 .

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)	28662	3-aminobenzonitrile	2237-30-1	C₇H₆N₂	详情	详情
(II)	14713	benzenesulfonyl chloride	98-09-9	C₆H₅ClO₂S	详情	详情
(III)	28663	N-(3-cyanophenyl)benzenesulfonamide		C₁₃H₁₀N₂O₂S	详情	详情
(IV)	28664	N-(5-cyano-2-nitrophenyl)benzenesulfonamide		C₁₃H₉N₃O₄S	详情	详情
(V)	28665	N-(2-amino-5-cyanophenyl)benzenesulfonamide		C₁₃H₁₁N₃O₂S	详情	详情
(VI)	28667	1,2-dichloro-3-isocyanatobenzene	41195-90-8	C₇H₃Cl₂NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

2,6-Dichlorobenzenethiol (I) is oxidized to the sulfonyl chloride (II) employing N-chlorosuccinimide. Subsequent treatment of acid chloride (II) with ammonia in cold pyridine provides sulfonamide (III). Reaction of (III) with HNO3 in the presence of concentrated H2SO4 leads to the nitro derivative (IV). Then, displacement of one chloride group of (IV) with potassium acetate in the presence of crown ether gives rise to the acetate ester (V), which is further hydrolyzed to phenol (VI) under acidic conditions. Nitro group reduction in (VI) with H2 and Pd/C affords aniline (VII). Finally, coupling of (VII) with 2,3-dichlorophenyl isocyanate (VIII) produces the title diaryl urea.

参考文献中间体

合成目标

【1】 Widdowson, K.L.; Jin, Q.; McCleland, B.W.; Palovich, M.R. (GlaxoSmithKline Inc.); Hydroxy diphenyl urea sulfonamides as IL-8 receptor antagonists. EP 1161232; JP 2002532419; US 6500863; WO 0035442 .

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)	33293	2,6-Dichloro thiophenol; 2,6-Dichlorobenzenethiol; 2,6-Dichlorophenylhydrosulfide	24966-39-0	C₆H₄Cl₂S	详情	详情
(II)	65084	2,6-dichlorobenzenesulfonyl chloride		C₆H₃Cl₃O₂S	详情	详情
(III)	65085	2,6-dichlorobenzenesulfonamide		C₆H₅Cl₂NO₂S	详情	详情
(IV)	65086	2,6-dichloro-3-nitrobenzenesulfonamide		C₆H₄Cl₂N₂O₄S	详情	详情
(V)	65087	2-(aminosulfonyl)-3-chloro-6-nitrophenyl acetate		C₈H₇ClN₂O₆S	详情	详情
(VI)	65088	6-chloro-2-hydroxy-3-nitrobenzenesulfonamide		C₆H₅ClN₂O₅S	详情	详情
(VII)	65089	3-amino-6-chloro-2-hydroxybenzenesulfonamide		C₆H₇ClN₂O₃S	详情	详情
(VIII)	28667	1,2-dichloro-3-isocyanatobenzene	41195-90-8	C₇H₃Cl₂NO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Aminopyrazole (III) was prepared by condensation of keto nitrile (I) with 3-nitrophenylhydrazine (II) in ethanolic HOAc. Subsequent reaction of (III) with 2,3-dichlorophenyl isocyanate (IV) in hot toluene produced the urea derivative (V). The nitro group of (V) was finally reduced to the title aniline by means of iron and acetic acid.

参考文献中间体

合成目标

【1】 Dumas, J.; Hatoum-Mokdad, H.; Sibley, R.; et al.; 1-Phenyl-5-pyrazolyl ureas: Potent and selective p38 kinase inhibitors. Bioorg Med Chem Lett 2000, 10, 18, 2051.
【2】 Ranges, G.E.; Bortolon, E.; Chau, T.; et al.; Pharmacological characterization of pyrazolyl urea p38 kinase inhibitors. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 149.
【3】 Dumas, J.; Bobko, M.; Bhargava, A.; et al.; Synthesis and SAR of p38 kinase inhibitors from the urea class. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 148.
【4】 Redman, A.; Smith, R.A.; Khire, U.; Wood, J.E.; Dumas, J.; Sibley, R.; Lowinger, T.B.; Scott, W.J.; Johnson, J.; Riedl, B.; Hatoum-Mokdad, H. (Bayer AG); Inhibition of p38 kinase activity using aryl and heteroaryl substd. heterocyclic ureas. WO 9932110 .

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)	44248	4,4-dimethyl-3-oxopentanenitrile	59997-51-2	C₇H₁₁NO	详情	详情
(II)	44249	1-(3-nitrophenyl)hydrazine		C₆H₇N₃O₂	详情	详情
(III)	44250	3-(tert-butyl)-1-(3-nitrophenyl)-1H-pyrazol-5-amine; 3-(tert-butyl)-1-(3-nitrophenyl)-1H-pyrazol-5-ylamine		C₁₃H₁₆N₄O₂	详情	详情
(IV)	28667	1,2-dichloro-3-isocyanatobenzene	41195-90-8	C₇H₃Cl₂NO	详情	详情
(V)	44251	N-[3-(tert-butyl)-1-(3-nitrophenyl)-1H-pyrazol-5-yl]-N'-(2,3-dichlorophenyl)urea		C₂₀H₁₉Cl₂N₅O₃	详情	详情

Extended Information