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【结 构 式】 
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【分子编号】65056 【品名】5-[(5-hydroxy-1,4,5,6-tetrahydro-2-pyrimidinyl)amino]nicotinic acid 【CA登记号】 |
【 分 子 式 】C10H12N4O3 【 分 子 量 】236.23044 【元素组成】C 50.84% H 5.12% N 23.72% O 20.32% |
合成路线1
该中间体在本合成路线中的序号：(XVI)5-Aminonicotinic acid (XII) is condensed with benzoyl isothiocyanate to form the benzoyl thiourea (XIII). Removal of the benzoyl group of (XIII) with NaOMe in MeOH, followed by alkylation with iodomethane, furnishes the S-methyl isothiourea (XIV). This is then condensed with 1,3-diamino-2-propanol (XV) in hot DMF, producing the tetrahydropyrimidine derivative (XVI). The carboxyl group of (XVI) is then activated as the mixed anhydride (XVII) employing isobutyl chloroformate and NMM. Coupling between anhydride (XVII) and amine (XI) in the presence of NMM leads to the diamide (XVIII). The ethyl ester group of (XVIII) is finally hydrolyzed by means of LiOH to the corresponding carboxylic acid.
| 【1】 Miyashiro, J.M.; Gasiecki, A.F.; Khanna, I.K.; Chandrakumar, N.S.; Desai, B.N.; Russell, M.A.; Devadas, B.; Rico, J.G.; Rogers, T.E.; Rao, S.N.; Malecha, J.W.; Ruminski, P.G.; Yu, Y.; Huff, R. (Pfizer Inc.); Heterocyclic glycyl beta-alanine derivs. as vitronectin antagonists. EP 1070060; JP 2002511462; WO 9952896 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 47974 | ethyl (3S)-3-[(2-aminoacetyl)amino]-3-(3,5-dichloro-2-hydroxyphenyl)propanoate | C13H16Cl2N2O4 | 详情 | 详情 | |
| (XII) | 65053 | 5-aminonicotinic acid | C6H6N2O2 | 详情 | 详情 | |
| (XIII) | 65054 | 5-{[(benzoylamino)carbothioyl]amino}nicotinic acid | C14H11N3O3S | 详情 | 详情 | |
| (XIV) | 65055 | 5-{[imino(methylsulfanyl)methyl]amino}nicotinic acid | C8H9N3O2S | 详情 | 详情 | |
| (XV) | 47975 | 1,3-diamino-2-propanol | 616-29-5 | C3H10N2O | 详情 | 详情 |
| (XVI) | 65056 | 5-[(5-hydroxy-1,4,5,6-tetrahydro-2-pyrimidinyl)amino]nicotinic acid | C10H12N4O3 | 详情 | 详情 | |
| (XVII) | 65057 | C15H20N4O5 | 详情 | 详情 | ||
| (XVIII) | 65058 | ethyl (3S)-3-(3,5-dichloro-2-hydroxyphenyl)-3-({2-[({5-[(5-hydroxy-1,4,5,6-tetrahydro-2-pyrimidinyl)amino]-3-pyridinyl}carbonyl)amino]acetyl}amino)propanoate | C23H26Cl2N6O6 | 详情 | 详情 |