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【结 构 式】

【分子编号】15803

【品名】methyl (2S,4R)-4-amino-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate

【CA登记号】

【 分 子 式 】C12H17N3O2

【 分 子 量 】235.286

【元素组成】C 61.26% H 7.28% N 17.86% O 13.6%

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:(XXIV)

2) The esterification of trans-4-hydroxy-L-proline (XVI) with SOCl2 and methanol gives the methyl ester (XVII), which is condensed with 3-(methanesulfonyloxymethyl)pyridine (XVIII), obtained by treatment of 3-(hydroxymethyl)pyridine (XIX) with methanesulfonyl chloride, by means of triethylamine yielding trans-N-(3-pyridylmethyl)-4-hydroxy-L-proline methyl ester (XX). The treatment of (XX) with methanesulfonyl chloride affords the corresponding mesylate (XXI), which by reaction with LiCl in hot polyethylene glycol gives cis-4-chloro-N-(3-pyridylmethyl)-L-proline methyl ester (XXII). The reaction of (XXII) with sodium azide in DMSO yields the trans-4-azido derivative (XXIII), which is reduced with triphenylphosphine in hot ethyl acetate to the corresponding trans-4-amino compound (XXIV). The treatment of (XXIV) with 4-chlorophenylsulfonyl chloride (VIII) and triethylamine in ethyl acetate affords the sulfonamide (XXV), which is reduced with diisobutylaluminum hydride in toluene/dichloromethane giving (2S,4R)-4-(4-chlorophenylsulfonamido)-1-(3-pyridylmethyl)pyrrolidine-2-carbaldehyde (XXVI). Finally, this compound is submitted to a Wittig condensation with (4-carboxybutyl)triphenylphosphonium chloride (XXVII) and potassium tert-butoxide in THF.

1 Graul, A.; Castaner, J.; KDI-792. Drugs Fut 1996, 21, 12, 1224.
2 Kagara, K.; Goto, S.; Yonishi, S.; Ikushima, M.; Baba, Y.; Horiai, H. (Fujisawa Pharmaceutical Co., Ltd.); Process for producing pyrrolidine deriv. and salt thereof. WO 9401400 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIII) 15787 4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride 98-60-2 C6H4Cl2O2S 详情 详情
(XVI) 14489 (2S,4R)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid; L-Hydroxyproline 51-35-4 C5H9NO3 详情 详情
(XVII) 15796 methyl (2S,4R)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylate C6H11NO3 详情 详情
(XVIII) 15797 3-pyridinylmethyl methanesulfonate C7H9NO3S 详情 详情
(XIX) 15798 3-Pyridinemethanol; 3-pyridinylmethanol 100-55-0 C6H7NO 详情 详情
(XX) 15799 methyl (2S,4R)-4-hydroxy-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate C12H16N2O3 详情 详情
(XXI) 15800 methyl (2S,4R)-4-[(methylsulfonyl)oxy]-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate C13H18N2O5S 详情 详情
(XXII) 15801 methyl (2S,4S)-4-chloro-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate C12H15ClN2O2 详情 详情
(XXIII) 15802 methyl (2S,4R)-4-azido-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate C12H15N5O2 详情 详情
(XXIV) 15803 methyl (2S,4R)-4-amino-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate C12H17N3O2 详情 详情
(XXV) 15804 methyl (2S,4R)-4-[[(4-chlorophenyl)sulfonyl]amino]-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrole-2-carboxylate C18H20ClN3O4S 详情 详情
(XXVI) 15805 4-chloro-N-[(3R,5S)-5-formyl-1-(3-pyridinylmethyl)tetrahydro-1H-pyrrol-3-yl]benzenesulfonamide C17H18ClN3O3S 详情 详情
(XXVII) 28718 (4-carboxybutyl)(triphenyl)phosphonium chloride C23H24ClO2P 详情 详情
Extended Information