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【结 构 式】 
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【分子编号】48582 【品名】(3aR,4S,6R,6aS)-6-[7-([(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]amino)-3H-imidazo[4,5-b]pyridin-3-yl]-N-ethyl-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxamide 【CA登记号】 |
【 分 子 式 】C25H32ClN5O3S 【 分 子 量 】518.07968 【元素组成】C 57.96% H 6.23% Cl 6.84% N 13.52% O 9.26% S 6.19% |
合成路线1
该中间体在本合成路线中的序号：(XII)An efficient synthesis of AMP-579 has been reported: Reaction of the chiral amine (I) with tosyl chloride and NaOH in methyl tert-butyl ether (MTBE) gives the tosyl aziridine (II), which is condensed with 3-chlorothiophene (III) by means of n-BuLi to yield the tosyl amide (IV). Condensation of amide (IV) with 2,4-difluoro-3-nitropyridine (V) obtained by reaction of 2,4-dichloro-3-nitropyridine (VI) with KF and 18-crown-6 (18-C-6) in hot 1-methyl-2-pyrrolidinone (NMP) by means of t-BuOK in THF affords the disubstituted tosyl amide (VII). Condensation of compound (VII) with the cyclopentanecarboxamide (VIII) by means of K2CO3 in NMP provides the corresponding adduct (IX), which is hydrogenated with H2 over Pt in methanol/ethyl acetate to give the aminopyridine (X). Cyclization of (X) with HC(OEt)3 by means of hot Ac2O yields the imidazopyridine (XI), which is detosylated with Mg in MeOH or LiEt3BH in THF to afford the protected deazapurine (XII). Finally, the acetonide group of (XII) is eliminated by treatment with concentrated HCl in THF.
| 【1】 O'Brien, M.K.; Powner, T.H.; Truesdale, L.K.; Kubiak, G.G.; Sledeski, A.W.; Powers, M.R.; Efficient synthesis of AMP579, a novel adenosine A1/A2 receptor agonist. J Org Chem 2000, 65, 23, 8114. |
| 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) | 48572 | (S)-(+)-2-Amino-1-butanol; L-(+)-2-Amino-1-butanol; (S)-2-Amino-1-butanol | 5856-62-2 | C4H11NO | 详情 | 详情 |
| (II) | 48573 | (2R)-2-ethyl-1-[(4-methylphenyl)sulfonyl]aziridine | C11H15NO2S | 详情 | 详情 | |
| (III) | 48574 | 3-Chlorothiophene; 3-Thienyl chloride | 17249-80-8 | C4H3ClS | 详情 | 详情 |
| (IV) | 48575 | N-[(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]-4-methylbenzenesulfonamide | C15H18ClNO2S2 | 详情 | 详情 | |
| (V) | 48576 | 2,4-difluoro-3-nitropyridine | C5H2F2N2O2 | 详情 | 详情 | |
| (VI) | 23847 | 2,4-dichloro-3-nitropyridine | C5H2Cl2N2O2 | 详情 | 详情 | |
| (VII) | 48577 | N-[(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]-N-(2-fluoro-3-nitro-4-pyridinyl)-4-methylbenzenesulfonamide | C20H19ClFN3O4S2 | 详情 | 详情 | |
| (VIII) | 48578 | (3aS,4R,6S,6aR)-6-[(ethylamino)carbonyl]-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-aminium benzoate | C18H26N2O5 | 详情 | 详情 | |
| (IX) | 48579 | (3aR,4S,6R,6aS)-6-[(4-[[(1R)-1-[(3-chloro-2-thienyl)methyl]propyl][(4-methylphenyl)sulfonyl]amino]-3-nitro-2-pyridinyl)amino]-N-ethyl-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxamide | C31H38ClN5O7S2 | 详情 | 详情 | |
| (X) | 48580 | (3aR,4S,6R,6aS)-6-[(3-amino-4-[[(1R)-1-[(3-chloro-2-thienyl)methyl]propyl][(4-methylphenyl)sulfonyl]amino]-2-pyridinyl)amino]-N-ethyl-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxamide | C31H40ClN5O5S2 | 详情 | 详情 | |
| (XI) | 48581 | (3aR,4S,6R,6aS)-6-(7-[[(1R)-1-[(3-chloro-2-thienyl)methyl]propyl][(4-methylphenyl)sulfonyl]amino]-3H-imidazo[4,5-b]pyridin-3-yl)-N-ethyl-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxamide | C32H38ClN5O5S2 | 详情 | 详情 | |
| (XII) | 48582 | (3aR,4S,6R,6aS)-6-[7-([(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]amino)-3H-imidazo[4,5-b]pyridin-3-yl]-N-ethyl-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxamide | C25H32ClN5O3S | 详情 | 详情 |