2-chloro-6-methylphenylamine; 2-chloro-6-methylaniline -Drug Synthesis Database

【结构式】

【分子编号】29789

【品名】2-chloro-6-methylphenylamine; 2-chloro-6-methylaniline

【CA登记号】87-63-8

【分子式】C₇H₈ClN

【分子量】141.59996

【元素组成】C 59.38% H 5.69% Cl 25.04% N 9.89%

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：(V)

Reaction of tert-butyl cyanoacetate (I) with ethyl mercaptoacetate (II) in the presence of potassium carbonate, followed by N-methylation and ester cleavage affords the intermediate carboxylic acid (III). This compound, by POCl3 in dimethylformamide or by Br2/TPP, is converted to the corresponding acid halogenide (IV), which is finally condensed with 2-chloro-6-methylaniline (V).

参考文献中间体

合成目标

【1】 Bartoszyk, G.; Hartenstein, J.; Herrmann, M.; Fritschi, E.; Satzinger, G. (Godecke AG); 4-Oxothiazolidin-2-ylideneacetamide derivatives as CNS agents. DE 3317000; EP 0124911; US 4563471 .
【2】 Satzinger, G.; Ralitoline. Drugs Fut 1985, 10, 11, 920.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IVa)	29787	2-(3-methyl-4-oxo-1,3-thiazolidin-2-ylidene)acetyl chloride		C₆H₆ClNO₂S	详情	详情
(IVb)	29788	2-(3-methyl-4-oxo-1,3-thiazolidin-2-ylidene)acetyl bromide		C₆H₆BrNO₂S	详情	详情
(I)	14330	tert-Butyl cyanoacetate; tert-butyl 2-cyanoacetate	1116-98-9	C₇H₁₁NO₂	详情	详情
(II)	23995	ethyl 2-sulfanylacetate	2713-34-0	C₄H₈O₂S	详情	详情
(III)	29786	2-(3-methyl-4-oxo-1,3-thiazolidin-2-ylidene)acetic acid		C₆H₇NO₃S	详情	详情
(V)	29789	2-chloro-6-methylphenylamine; 2-chloro-6-methylaniline	87-63-8	C₇H₈ClN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Reaction of ethyl 4-aminobenzoate (I) with sodium thiocyanate and bromine in cold AcOH gives rise to the amino benzothiazole (II). Subsequent treatment of (II) with phenyl chloroformate affords the phenyl carbamate (III), which is further reacted with tert-butylamine to furnish urea (IV). After alkaline hydrolysis of the ethyl ester (IV), the resultant carboxylic acid (V) is converted to the azabenzotriazolyl active ester (VI) upon treatment with HATU in DMF. Active ester (VI) is finally coupled with 2-chloro-6-methylaniline (VII) in the presence of sodium bis(trimethylsilyl)amide to yield the target amide.

参考文献中间体

合成目标

【1】 Das, J.; Barrish, J.C.; Wityak, J. (Bristol-Myers Squibb Co.); Benzothiazole protein tyrosine kinase inhibitors. EP 1037632; JP 2001522800; WO 9924035 .

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)	16498	Benzocaine; ethyl 4-aminobenzoate	94-09-7	C₉H₁₁NO₂	详情	详情
(II)	65034	ethyl 2-amino-1,3-benzothiazole-6-carboxylate		C₁₀H₁₀N₂O₂S	详情	详情
(III)	65035	ethyl 2-[(phenoxycarbonyl)amino]-1,3-benzothiazole-6-carboxylate		C₁₇H₁₄N₂O₄S	详情	详情
(IV)	65036	ethyl 2-{[(tert-butylamino)carbonyl]amino}-1,3-benzothiazole-6-carboxylate		C₁₅H₁₉N₃O₃S	详情	详情
(V)	65037	2-{[(tert-butylamino)carbonyl]amino}-1,3-benzothiazole-6-carboxylic acid		C₁₃H₁₅N₃O₃S	详情	详情
(VI)	65038	N-(tert-butyl)-N'-{6-[(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)carbonyl]-1,3-benzothiazol-2-yl}urea		C₁₈H₁₇N₇O₃S	详情	详情
(VII)	29789	2-chloro-6-methylphenylamine; 2-chloro-6-methylaniline	87-63-8	C₇H₈ClN	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Chen B-C,DroghiniR,et aL 2006.Process for preparing 2-aminothiazole-5-carboxamides from thioureas and acrylamides and their use as anticancer drugs. US 2006004067

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（V)	32323	4,6-dichloro-2-methylpyrimidine	1780-26-3	C₅H₄Cl₂N₂	详情	详情
(I)	29789	2-chloro-6-methylphenylamine; 2-chloro-6-methylaniline	87-63-8	C₇H₈ClN	详情	详情
(II)	20616	(E)-3-ethoxy-2-propenoyl chloride	99471-66-6	C₅H₇ClO₂	详情	详情
(III)	66243	(E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide	863127-76-8	C₁₂H₁₄ClNO₂	详情	详情
(IV)	66244	2-amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide	302964-24-5	C₁₁H₁₀ClN₃OS	详情	详情
(VI)	66245	2-((6-chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazolidine-5-carboxamide		C₁₆H₁₇Cl₂N₅OS	详情	详情
(VII)	21893	2-(1-piperazinyl)-1-ethanol; 1-piperazineethanol; 1-(2-Hydroxyethyl)piperazine	103-76-4	C₆H₁₄N₂O	详情	详情

Extended Information