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【结 构 式】 
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【药物名称】BMS-431051 【化学名称】N-[5-[3-(4-Acetylpiperazin-1-ylcarbonyl)-5-aminobenzylsulfanyl]thiazol-2-yl]-4-(dimethylamino)benzamide 【CA登记号】 【 分 子 式 】C26H30N6O3S2 【 分 子 量 】538.6954 |
【开发单位】Bristol-Myers Squibb (Originator) 【药理作用】Antiarthritic Drugs, Asthma Therapy, IMMUNOMODULATING AGENTS, RESPIRATORY DRUGS, Rheumatoid Arthritis, Treatment of, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Treatment of Transplant Rejection, ITK (EMT) Kinase Inhibitors |
合成路线1
The reductocondensation of 3-amino-5-(chloromethyl)benzoic acid methyl ester (I) with 2-aminothiazol-5-ylisothiocyanate (II) by means of NaBH4 gives the thioether (III), which is condensed with 4-(dimethylamino)benzoyl chloride (IV) by means of pyridine in dichloromethane to yield the amide (V). The hydrolysis of the ester group of (V) with NaOH in methanol affords the corresponding carboxylic acid (VI), which is finally condensed with 1-acetylpiperazine (VII) by means of WSC, HATU and DIEA in THF to provide the target piperazide.
| 【1】 Wityak, J.; Das, J.; Liu, C.; Lin, J.; Spergel, S.H.; Moquin, R.V.; Furch, J.A.; Doweiko, A.; Kanner, S.; Lin, T.-A.; Selective Emt inhibitors: Discovery and SAR of 2-amino-[(5-thiomethyl)aryl]thiazoles. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 257. |
| 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) | 64135 | methyl 3-amino-5-(chloromethyl)benzoate | C9H10ClNO2 | 详情 | 详情 | |
| (II) | 64136 | 2-amino-1,3-thiazole-5-sulfenyl cyanide | 23056-10-2 | C4H3N3S2 | 详情 | 详情 |
| (III) | 64137 | methyl 3-amino-5-{[(2-amino-1,3-thiazol-5-yl)sulfanyl]methyl}benzoate | C12H13N3O2S2 | 详情 | 详情 | |
| (IV) | 39988 | 4-(dimethylamino)benzoyl chloride | 4755-50-4 | C9H10ClNO | 详情 | 详情 |
| (V) | 64138 | methyl 3-amino-5-{[(2-{[4-(dimethylamino)benzoyl]amino}-1,3-thiazol-5-yl)sulfanyl]methyl}benzoate | C21H22N4O3S2 | 详情 | 详情 | |
| (VI) | 64139 | 3-amino-5-{[(2-{[4-(dimethylamino)benzoyl]amino}-1,3-thiazol-5-yl)sulfanyl]methyl}benzoic acid | C20H20N4O3S2 | 详情 | 详情 | |
| (VII) | 20674 | N-Acetyl piperazine; 1-(1-piperazinyl)-1-ethanone | 13889-98-0 | C6H12N2O | 详情 | 详情 |