【结 构 式】 |
【分子编号】65034 【品名】ethyl 2-amino-1,3-benzothiazole-6-carboxylate 【CA登记号】 |
【 分 子 式 】C10H10N2O2S 【 分 子 量 】222.26768 【元素组成】C 54.04% H 4.53% N 12.6% O 14.4% S 14.43% |
合成路线1
该中间体在本合成路线中的序号:(II)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.
【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2
该中间体在本合成路线中的序号:(II)In an alternative method, ethyl 4-aminobenzoate (I) is treated with NaSCN/Br2 to produce the amino benzothiazole (II), which is further protected as the N-Boc derivative (III). Alkaline hydrolysis of ester (III), followed by chlorination of the resultant acid (IV) with oxalyl chloride gives rise to the acid chloride (V). This is then coupled with 2-chloro-6-methylaniline (VI) yielding amide (VII). The N-Boc protecting group of (VII) is then cleaved employing trifluoroacetic acid to produce amine (VIII), which is subsequently reacted with phenyl chloroformate producing the phenyl carbamate (IX). Finally, displacement of carbamate (IX) with tert-butylamine furnishes the title urea. (1,2)
【1】 Das, J.; Lin, J.; Moquin, R.V.; Shen, Z.; Spergel, S.H.; Wityak, J.; Doweyko, A.M.; DeFex, H.F.; Fang, Q.; Pang, S.; Pitt, S.; Shen, D.R.; Schieven, G.L.; Barrish, J.C.; Molecular design, synthesis, and structure-activity relationships leading to the potent and selective p56(lck) inhibitor BMS-243117. Bioorg Med Chem Lett 2003, 13, 13, 2145. |
【2】 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) | 65039 | ethyl 2-[(tert-butoxycarbonyl)amino]-1,3-benzothiazole-6-carboxylate | C15H18N2O4S | 详情 | 详情 | |
(IV) | 65040 | 2-[(tert-butoxycarbonyl)amino]-1,3-benzothiazole-6-carboxylic acid | C13H14N2O4S | 详情 | 详情 | |
(V) | 65041 | tert-butyl 6-(chlorocarbonyl)-1,3-benzothiazol-2-ylcarbamate | C13H13ClN2O3S | 详情 | 详情 | |
(VI) | 29787 | 2-(3-methyl-4-oxo-1,3-thiazolidin-2-ylidene)acetyl chloride | C6H6ClNO2S | 详情 | 详情 | |
(VII) | 65042 | tert-butyl 6-[(2-chloro-6-methylanilino)carbonyl]-1,3-benzothiazol-2-ylcarbamate | C20H20ClN3O3S | 详情 | 详情 | |
(VIII) | 65043 | 2-amino-N-(2-chloro-6-methylphenyl)-1,3-benzothiazole-6-carboxamide | C15H12ClN3OS | 详情 | 详情 | |
(IX) | 65044 | phenyl 6-[(2-chloro-6-methylanilino)carbonyl]-1,3-benzothiazol-2-ylcarbamate | C22H16ClN3O3S | 详情 | 详情 |