【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% |
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 |