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【结 构 式】 
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【分子编号】59508 【品名】5-{2-[(6S)-2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimido[5,4-b][1,4]thiazin-6-yl]ethyl}-2-thiophenecarboxylic acid 【CA登记号】 |
【 分 子 式 】C13H14N4O3S2 【 分 子 量 】338.41132 【元素组成】C 46.14% H 4.17% N 16.56% O 14.18% S 18.95% |
合成路线1
该中间体在本合成路线中的序号：(XIX)After removal of the Boc protecting group of (XIV), the resultant free amine spontaneously cyclized to the lactam (XV) in methanolic solution. Lactam (XV) was O-alkylated with trimethyloxonium fluoroborate, yielding the lactim ether (XVI), which was condensed with guanidine (XVII) to produce the pyridothiazine (XVIII). Hydrolysis of the ethyl ester of (XVIII), followed by coupling of the resultant acid (XIX) with L-glutamic acid diethyl ester (XX), furnished amide (XXI). The ester groups of (XXI) were finally hydrolyzed with NaOH to give the title compound.
| 【1】 Varney, M.D.; et al.; Protein structure-based design, synthesis, and biological evaluation of 5-thia-2, 6-diamino-4(3H)-oxopyrimidines: Potent inhibitors of glycinamide ribonucleotide transformylase with potent cell growth inhibition. J Med Chem 1997, 40, 16, 2502. |
| 【2】 Varney, M.D.; Palmer, C.L.; Romines, W.H. (Agouron Pharmaceuticals, Inc.); Syntheses of optically pure cpds. useful as GARFT inhibitors and their intermediates. WO 9640674 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 59504 | dimethyl 2-({(1S)-1-{[(tert-butoxycarbonyl)amino]methyl}-3-[5-(ethoxycarbonyl)-2-thienyl]propyl}sulfanyl)malonate | C21H31NO8S2 | 详情 | 详情 | |
| (XV) | 59505 | methyl (6S)-6-{2-[5-(ethoxycarbonyl)-2-thienyl]ethyl}-3-oxo-2-thiomorpholinecarboxylate | C15H19NO5S2 | 详情 | 详情 | |
| (XVI) | 59506 | methyl (6S)-6-{2-[5-(ethoxycarbonyl)-2-thienyl]ethyl}-3-methoxy-5,6-dihydro-2H-1,4-thiazine-2-carboxylate | C16H21NO5S2 | 详情 | 详情 | |
| (XVII) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
| (XVIII) | 59507 | ethyl 5-{2-[(6S)-2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimido[5,4-b][1,4]thiazin-6-yl]ethyl}-2-thiophenecarboxylate | C15H18N4O3S2 | 详情 | 详情 | |
| (XIX) | 59508 | 5-{2-[(6S)-2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimido[5,4-b][1,4]thiazin-6-yl]ethyl}-2-thiophenecarboxylic acid | C13H14N4O3S2 | 详情 | 详情 | |
| (XX) | 11013 | diethyl (2S)-2-aminopentanedioate | C9H17NO4 | 详情 | 详情 | |
| (XXI) | 59509 | diethyl (2S)-2-{[(5-{2-[(6S)-2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimido[5,4-b][1,4]thiazin-6-yl]ethyl}-2-thienyl)carbonyl]amino}pentanedioate | C22H29N5O6S2 | 详情 | 详情 |