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【结 构 式】

【分子编号】40493

【品名】(1S,2R,3S,4R)-4-[[3-amino-4-([(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]amino)-2-pyridinyl]amino]-N-ethyl-2,3-dihydroxycyclopentanecarboxamide

【CA登记号】

【 分 子 式 】C21H30ClN5O3S

【 分 子 量 】468.0198

【元素组成】C 53.89% H 6.46% Cl 7.58% N 14.96% O 10.26% S 6.85%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XV)

Reaction of 2-hydroxy-4-methoxypyridine-3-carbonitrile (X) with 85% phosphoric acid at 180 C gives 2,4-dihydroxypyridine (XI), which is nitrated with HNO3 in hot acetic acid to yield 2,4-dihydroxy-3-nitropyridine (XII). The reaction of (XII) with POCl3 in hot toluene affords 4-chloro-3-nitropyridin-2(1H)-one (XIII), which is condensed with the previously described amine (II) by means of DIEA in isopropanol to afford the aminopyridinol (XIV). Chlorination of (XIV) with POCl3 in toluene gives the previously described 4-amino-2-chloro-3-nitropyridine derivative (III), which is condensed with the described cyclopentanecarboxamide (IV) by means of K2CO3 in toluene, yielding the already known 2,4-diamino-3-nitropyridine (V). The reduction of (V) with ammonium formate over Pt/C or with Zn and ammonium acetate affords the described 2,3,4-triaminopyridine (VI), which is treated with HCl in THF in order to eliminate the acetonide group, providing the deprotected triaminopyridine derivative (XV). Finally, this compound is cyclized with formamidine (VII), triethyl orthoformate (XVI) or dimethylformamide dimethylacetal (XVII) in a suitable solvent.

1 Martín, L.; Leeson, P.A.; Castañer, J.; Sorbera, L.A.; AMP-579. Drugs Fut 2000, 25, 9, 900.
2 Reilly, L.W.; Vanasse, B.J.; Garcia, H.; Shah, H.C.; Leon, P.; O'Brien, M.K.; Walther, F.L.; Powner, T.H.; Tsuei, C.T.; Thompson, M.D. (Aventis Pharmaceuticals, Inc.); Preparation of [1S-[1a,2b,3b,4a(S*)]]-4-[7-[[1-(3-chloro-2-thienyl)methyl]propyl]amino]-3H-imidazo[4,5-b]pyridin-3-yl]N-ethyl-2,3-dihydroxycyclopentanecarboxamide. WO 9825921 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(III) 23849 N-(2-chloro-3-nitro-4-pyridinyl)-N-[(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]amine; 2-chloro-N-[(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]-3-nitro-4-pyridinamine C13H13Cl2N3O2S 详情 详情
(IV) 23850 (3aR,4S,6R,6aS)-6-amino-N-ethyl-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxamide C11H20N2O3 详情 详情
(V) 23851 (3aR,4S,6R,6aS)-6-[[4-([(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]amino)-3-nitro-2-pyridinyl]amino]-N-ethyl-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxamide C24H32ClN5O5S 详情 详情
(VI) 23848 (2R)-1-(3-chloro-2-thienyl)-2-butanamine; (1R)-1-[(3-chloro-2-thienyl)methyl]propylamine C8H12ClNS 详情 详情
(VI) 23852 (3aR,4S,6R,6aS)-6-[[3-amino-4-([(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]amino)-2-pyridinyl]amino]-N-ethyl-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxamide C24H34ClN5O3S 详情 详情
(VII) 15369 Iminoformamide; Methanimidamide 463-52-5 CH4N2 详情 详情
(X) 40489 2-hydroxy-4-methoxynicotinonitrile C7H6N2O2 详情 详情
(XI) 34269 2,4-pyridinediol 626-03-9 C5H5NO2 详情 详情
(XII) 40490 3-nitro-2,4-pyridinediol 89282-12-2 C5H4N2O4 详情 详情
(XIII) 40491 4-chloro-3-nitro-2(1H)-pyridinone C5H3ClN2O3 详情 详情
(XIV) 40492 4-([(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]amino)-3-nitro-2-pyridinol C13H14ClN3O3S 详情 详情
(XV) 40493 (1S,2R,3S,4R)-4-[[3-amino-4-([(1R)-1-[(3-chloro-2-thienyl)methyl]propyl]amino)-2-pyridinyl]amino]-N-ethyl-2,3-dihydroxycyclopentanecarboxamide C21H30ClN5O3S 详情 详情
(XVI) 21304 Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether 122-51-0 C7H16O3 详情 详情
(XVII) 11984 N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine; Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal 4637-24-5 C5H13NO2 详情 详情
Extended Information