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【结 构 式】

【分子编号】65707

【品名】(S)-1-(tert-Butoxycarbonyl)-2,5-dihydro-1H-pyrrole-2-carboxylic acid; Boc-3,4-Dehydro-Pro-OH

【CA登记号】51154-06-4

【 分 子 式 】C10H15NO4

【 分 子 量 】213.23344

【元素组成】C 56.33% H 7.09% N 6.57% O 30.01%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XXXIV)

The bicyclic carboxamide (V) can be obtained as follows. Esterification of L-pyroglutamic acid (XXIX) with ethanolic H2SO4 followed by protection with Boc2O gives 1-Boc-5-oxoproline ethyl ester (XXXI). After reduction of (XXXI) with LiBHEt3, the obtained hemiaminal (XXXII) is dehydrated to the dehydroproline derivative (XXXIII) employing trifluoroacetic anhydride, DMAP and DIEA. Subsequent hydrolysis of ethyl ester (XXXIII) by means of LiOH leads to the carboxylic acid (XXXIV), which is converted to the corresponding carboxamide (XXXV) via activation with methanesulfonyl chloride, followed by reaction with ammonia. Simmons-Smith cyclopropanation of (XXXV) using diiodomethane and diethylzinc gives the bicyclic derivative (XXXVI), which is then deprotected under acidic conditions to furnish (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide (V) (2, 3). Scheme 4.

2 Vu, T.C., Hamann, L.G., Fox, R. et al. (Bristol-Myers Squibb Co.). Methods and compounds producing dipeptidyl peptidase IV inhibitors and intermediates thereof. JP 200651621, US 2005090539, WO 2004052850.
3 Politino, M., Cadin, M.M., Skonezny, P.M., Chen, J.G. (Bristol-Myers Squibb Co.). EP 1737970, JP 2007532137, WO 2005106011.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 65682 (1S,3S,5S)-2-Azabicyclo[3.1.0]hexane-3-carboxamide 361440-68-8 C6H10N2O 详情 详情
(XXIX) 32406 (2S)-5-oxo-2-pyrrolidinecarboxylic acid 98-79-3 C5H7NO3 详情 详情
(XXX) 65704 Ethyl L-pyroglutamate; Ethyl 5-oxo-L-prolinate; Ethyl (S)-(+)-2-pyrrolidone-5-carboxylate; 5-Oxo-proline ethyl ester; L(+)-Pyroglutamic acid ethyl ester 7149-65-7 C7H11NO3 详情 详情
(XXXI) 43914 1-(tert-butyl) 2-ethyl (2S)-5-oxo-1,2-pyrrolidinedicarboxylate 144978-35-8 C12H19NO5 详情 详情
(XXXII) 65705     C12H21NO5 详情 详情
(XXXIII) 65706 (S)-1-Boc-2,3-dihydro-2-pyrrolecarboxylic acid ethyl ester; (S)-1-tert-Butyl 2-ethyl 2,3-dihydro-1H-pyrrole-1,2-dicarboxylate; Ethyl N-Boc-L-proline-4-ene 178172-26-4 C12H19NO4 详情 详情
(XXXIV) 65707 (S)-1-(tert-Butoxycarbonyl)-2,5-dihydro-1H-pyrrole-2-carboxylic acid; Boc-3,4-Dehydro-Pro-OH 51154-06-4 C10H15NO4 详情 详情
(XXXV) 65708 (2S)-2-(Aminocarbonyl)-2,3-dihydro-1H-pyrrole-1-carboxylic acid 1,1-dimethylethyl ester 709031-38-9 C10H16N2O3 详情 详情
(XXXVI) 65709 (1S,3S,5S)-3-(Aminocarbonyl)-2-azabicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester 361440-67-7 C11H18N2O3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

 

中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 65708 (2S)-2-(Aminocarbonyl)-2,3-dihydro-1H-pyrrole-1-carboxylic acid 1,1-dimethylethyl ester 709031-38-9 C10H16N2O3 详情 详情
(VIII) 67425 (1S,3S,5S)-2-Azabicyclo[3.1.0]hexane-3-carboxamide methanesulfonate   C6H10N2O.CH4O3S 详情 详情
(I) 32406 (2S)-5-oxo-2-pyrrolidinecarboxylic acid 98-79-3 C5H7NO3 详情 详情
(II) 65704 Ethyl L-pyroglutamate; Ethyl 5-oxo-L-prolinate; Ethyl (S)-(+)-2-pyrrolidone-5-carboxylate; 5-Oxo-proline ethyl ester; L(+)-Pyroglutamic acid ethyl ester 7149-65-7 C7H11NO3 详情 详情
(III) 43914 1-(tert-butyl) 2-ethyl (2S)-5-oxo-1,2-pyrrolidinedicarboxylate 144978-35-8 C12H19NO5 详情 详情
(IV) 65706 (S)-1-Boc-2,3-dihydro-2-pyrrolecarboxylic acid ethyl ester; (S)-1-tert-Butyl 2-ethyl 2,3-dihydro-1H-pyrrole-1,2-dicarboxylate; Ethyl N-Boc-L-proline-4-ene 178172-26-4 C12H19NO4 详情 详情
(V) 65707 (S)-1-(tert-Butoxycarbonyl)-2,5-dihydro-1H-pyrrole-2-carboxylic acid; Boc-3,4-Dehydro-Pro-OH 51154-06-4 C10H15NO4 详情 详情
Extended Information