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【结 构 式】 
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【分子编号】47978 【品名】tert-butyl 5-hydroxy-2-(methylsulfanyl)-5,6-dihydro-1(4H)-pyrimidinecarboxylate 【CA登记号】 |
【 分 子 式 】C10H18N2O3S 【 分 子 量 】246.3306 【元素组成】C 48.76% H 7.37% N 11.37% O 19.49% S 13.02% |
合成路线1
该中间体在本合成路线中的序号：(XVI)The condensation of 1,3-diamino-2-propanol (XIII) with carbon disulfide produced 5-hydroxytetrahydropyrimidine-2-thione (XIV). Alkylation of thione (XIV) with iodomethane gave the cyclic S-methylisothiourea (XV), which was further protected as the N-Boc derivative (XVI). 3-Amino-5-hydroxybenzoic acid (XVIII) was prepared from 3,5-dihydroxybenzoic acid (XVII) by treatment with ammonia and ammonium chloride. Coupling of thioether (XVI) with amino acid (XVIII) in hot DMA furnished the guanidine adduct (XIX). This was then condensed with the intermediate (XII) via activation as the mixed anhydride with isobutyl chloroformate, producing amide (XX). Acid cleavage of the Boc group of (XX) gave (XXI). The ethyl ester of (XXI) was then hydrolyzed using NaOH in aqueous dioxan. The title compound was finally isolated as the hydrochloride salt after lyophilization from an HCl solution.
| 【2】 Ruminski, P.G.; Rogers, T.E. (Pharmacia Corp.); Meta-azacyclic amino benzoic acid cpds. and derivs. thereof being integrin antagonists. EP 1060164; WO 9944994 . |
| 【3】 Gordon, G.B.; Ruminski, P.G.; Nickols, G.A.; Westlin, W.F.; Rogers, T.E.; Cunningham, J. (Pharmacia Corp.); Use of integrin antagonist and a chemotherapeutic agent in the treatment of neoplasia. WO 0051686 . |
| 【1】 Ruminski, P.G.; Clare, M.; Collins, P.W.; Desai, B.N.; Lindmark, R.J.; Rico, J.G.; Rogers, T.E.; Russell, M.A. (Pharmacia Corp.); Meta-guanidine, urea, thiourea or azacyclic amino benzoic acid derivs. as integrin antagonists. EP 0850221; JP 1999510814; US 6013651; WO 9708145 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 47974 | ethyl (3S)-3-[(2-aminoacetyl)amino]-3-(3,5-dichloro-2-hydroxyphenyl)propanoate | C13H16Cl2N2O4 | 详情 | 详情 | |
| (XIII) | 47975 | 1,3-diamino-2-propanol | 616-29-5 | C3H10N2O | 详情 | 详情 |
| (XIV) | 47976 | 5-hydroxytetrahydro-2(1H)-pyrimidinethione | C4H8N2OS | 详情 | 详情 | |
| (XV) | 47977 | 2-(methylsulfanyl)-1,4,5,6-tetrahydro-5-pyrimidinol | C5H10N2OS | 详情 | 详情 | |
| (XVI) | 47978 | tert-butyl 5-hydroxy-2-(methylsulfanyl)-5,6-dihydro-1(4H)-pyrimidinecarboxylate | C10H18N2O3S | 详情 | 详情 | |
| (XVII) | 16230 | resorcylic acid; 3,5-dihydroxybenzoic acid | 99-10-5 | C7H6O4 | 详情 | 详情 |
| (XVIII) | 47979 | 3-amino-5-hydroxybenzoic acid | C7H7NO3 | 详情 | 详情 | |
| (XIX) | 47980 | 3-[[1-(tert-butoxycarbonyl)-5-hydroxy-1,4,5,6-tetrahydro-2-pyrimidinyl]amino]-5-hydroxybenzoic acid | C16H21N3O6 | 详情 | 详情 | |
| (XX) | 47981 | tert-butyl 2-(3-[[(2-[[(1S)-1-(3,5-dichloro-2-hydroxyphenyl)-3-ethoxy-3-oxopropyl]amino]-2-oxoethyl)amino]carbonyl]-5-hydroxyanilino)-5-hydroxy-5,6-dihydro-1(4H)-pyrimidinecarboxylate | C29H35Cl2N5O9 | 详情 | 详情 | |
| (XXI) | 47982 | ethyl (3S)-3-(3,5-dichloro-2-hydroxyphenyl)-3-[[2-([3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydro-2-pyrimidinyl)amino]benzoyl]amino)acetyl]amino]propanoate | C24H27Cl2N5O7 | 详情 | 详情 |