2-chloro-5-nitroaniline; 2-chloro-5-nitrophenylamine -Drug Synthesis Database

【结构式】

【分子编号】43033

【品名】2-chloro-5-nitroaniline; 2-chloro-5-nitrophenylamine

【CA登记号】6283-25-6

【分子式】C₆H₅ClN₂O₂

【分子量】172.57068

【元素组成】C 41.76% H 2.92% Cl 20.54% N 16.23% O 18.54%

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：(I)

The reaction of 2-chloro-5-nitroaniline (I) with NaNO2 in HCl and HOAc, followed by addition of CuCl2 and SO2 yields sulfonyl chloride (II). Reaction of (II) with NH4OH affords sulfonamide (III), which is then treated 3-methylaniline (IV) in 3-chlorotoluene to furnish intermediate (V). Final conversion of (V) into the target product is achieved by treatment in H2O/acetone with NaOH and carbamimidothioate (VIII), which can be obtained by reaction of dimethyl N-cyanodithioiminocarbonate (VI) with amine (VII) in EtOH.

参考文献中间体

合成目标

【1】 Delarge, J.; Masereel, B.; Dogne, J.-M. (University of Liege); Benzenic sulphonamide derivs. and their uses. WO 0042004 .

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)	43033	2-chloro-5-nitroaniline; 2-chloro-5-nitrophenylamine	6283-25-6	C₆H₅ClN₂O₂	详情	详情
(II)	43034	2-chloro-5-nitrobenzenesulfonyl chloride;2-Chloro-5-nitro-benzenesulfonyl chloride;2-Chloro-5-nitrophenylsulfonyl chloride;6-Chloro-3-nitrobenzenesulfonyl chloride	4533-95-3	C₆H₃Cl₂NO₄S	详情	详情
(III)	43035	2-chloro-5-nitrobenzenesulfonamide	96-72-0	C₆H₅ClN₂O₄S	详情	详情
(IV)	30687	3-methylphenylamine; m-toluidine	108-44-1	C₇H₉N	详情	详情
(V)	43036	5-nitro-2-(3-toluidino)benzenesulfonamide		C₁₃H₁₃N₃O₄S	详情	详情
(VI)	43037	[[bis(methylsulfanyl)methylene]amino]methane		C₄H₉NS₂	详情	详情
(VII)	18672	azepane	111-49-9	C₆H₁₃N	详情	详情
(VIII)	43038	methyl N-cyano-1-azepanecarbimidothioate		C₉H₁₅N₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Diazotization of 2-chloro-5-nitroaniline (I), followed by quenching with a solution of SO2 in HOAc in the presence of CuCl2, furnished the sulfonyl chloride (II). Treatment of (II) with aqueous ammonia gave rise to the corresponding sulfonamide (III). The chloro group of (III) was then displaced with cyclohexylamine (IV) in refluxing 3-chlorotoluene to afford the cyclohexylamino benzenesulfonamide (V). Finally, condensation of sulfonamide (V) with pentyl isocyanate (VI) produced the target sulfonylurea.

参考文献中间体

合成目标

【1】 Delarge, J.; Masereel, B.; Dogne, J.-M. (University of Liege); Benzenic sulphonamide derivs. and their uses. WO 0042004 .

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)	43033	2-chloro-5-nitroaniline; 2-chloro-5-nitrophenylamine	6283-25-6	C₆H₅ClN₂O₂	详情	详情
(II)	43034	2-chloro-5-nitrobenzenesulfonyl chloride;2-Chloro-5-nitro-benzenesulfonyl chloride;2-Chloro-5-nitrophenylsulfonyl chloride;6-Chloro-3-nitrobenzenesulfonyl chloride	4533-95-3	C₆H₃Cl₂NO₄S	详情	详情
(III)	43035	2-chloro-5-nitrobenzenesulfonamide	96-72-0	C₆H₅ClN₂O₄S	详情	详情
(IV)	17966	cyclohexanamine; cyclohexyl amine; cyclohexylamine	108-91-8	C₆H₁₃N	详情	详情
(V)	47439	2-(cyclohexylamino)-5-nitrobenzenesulfonamide		C₁₂H₁₇N₃O₄S	详情	详情
(VI)	47440	1-isocyanatopentane; pentyl isocyanate	3954-13-0	C₆H₁₁NO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Sandmeyer reaction of 2-chloro-5-nitroaniline (I) with NaNO2 in the presence of KI gives 1-chloro-2-iodo-4-nitrobenzene (II), which is then coupled with (2-pyridyl)zinc iodide (III) by means of Pd(PPh3)4, tris(2-furyl)phosphine and CuI in THF/DMAc to provide the phenylpyridine derivative (IV). After nitro group reduction in compound (IV) using either Fe and AcOH at 80 °C or SnCl2 and HCl in EtOH , the resulting pyridylaniline (V) is finally acylated with either 2-chloro-4-(methylsulfonyl)benzoyl chloride (VI) in the presence of Et3N in CH2Cl2 or 2-chloro-4-(methylsulfonyl)benzoic acid (VII) by means of HATU and DIEA in DMF .

参考文献中间体

合成目标

【1】 Robarge, K.D., Brunton, S.A., Castanedo, G.M. et al. GDC-0449 - A potent inhibitor of the hedgehog pathway. Bioorg Med Chem Lett 2009, 19(19): 5576-81.
【2】 Gunzner, J., Sutherlin, D., Stanley, M. et al. (Genentech, Inc.; Curis, Inc.). Pyridyl inhibitors of hedgehog signalling. EP 1789390, JP 2008511675, WO 2006028958.

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)	43033	2-chloro-5-nitroaniline; 2-chloro-5-nitrophenylamine	6283-25-6	C₆H₅ClN₂O₂	详情	详情
(II)	69162	1-chloro-2-iodo-4-nitrobenzene;4-Chloro-3-iodonitrobenzene	74534-15-9	C₆H₃ClINO₂	详情	详情
(III)	69164	(2-pyridyl)zinc iodide		C₅H₄INZn	详情	详情
(IV)	69163	2-(2-chloro-5-nitrophenyl)pyridine		C₁₁H₇ClN₂O₂	详情	详情
(V)	69165	4-chloro-3-(pyridin-2-yl)aniline		C₁₁H₉ClN₂	详情	详情
(VI)	69166	2-chloro-4-(methylsulfonyl)benzoyl chloride;2-chloro-5-(methylsulfonyl)benzoyl chloride		C₈H₆Cl₂O₃S	详情	详情
(VII)	69167	2-chloro-4-(methylsulfonyl)benzoic acid;2-chloro-5-(methylsulfonyl)benzoic acid	89938-62-5	C₈H₇ClO₄S	详情	详情

Extended Information