(R)-2-(5-Amino-2-chloro-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester → [4-Chloro-3-((R)-1-pyrrolidin-2-ylmethoxy)-phenyl]-{7-[3-(propane-2-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-yl}-amine
반응식
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[C:19]([NH2:21])[CH:18]=[CH:17][C:16]=1[Cl:22])=O)(C)(C)C.[CH3:23][CH:24]([S:26]([C:29]1[CH:30]=[C:31]([C:35]2[N:43]3[C:38]([CH:39]=[N:40][C:41](O)=[N:42]3)=[CH:37][CH:36]=2)[CH:32]=[CH:33][CH:34]=1)(=[O:28])=[O:27])[CH3:25]>>[Cl:22][C:16]1[CH:17]=[CH:18][C:19]([NH:21][C:41]2[N:40]=[CH:39][C:38]3=[CH:37][CH:36]=[C:35]([C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([S:26]([CH:24]([CH3:25])[CH3:23])(=[O:28])=[O:27])[CH:30]=4)[N:43]3[N:42]=2)=[CH:20][C:15]=1[O:14][CH2:13][C@H:9]1[CH2:10][CH2:11][CH2:12][NH:8]1참가 물질
3
실험 절차
This example was prepared by using (R)-2-(5-Amino-2-chloro-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (J. Med. Chem. 2007, 50, 4353) and 7-[3-(Propane-2-sulfonyl)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ol as described in Example 1255c followed by deprotection as described in Example 1223. 1H-NMR (DMSO) δ 9.7 (s, 1H), 9.5 (brs, 1H), 9 (s, 1H), 8.9 (brs, 1H), 8.5 (s, 1H), 8.4 (d, (d, J=7.5 Hz, 1H), 7.8 (m, 2H), 7.5 (d, J=8.7 Hz, 1H), 7.4 (m, 2H), 7.3 (d, J=4.8 Hz, 1H), 7 (d, J=4.8 Hz, 1H), 4.1 (m, 1H), 4.0 (m, 1H), 3.0 (brs, 1H), 3.5 (m, 2H), 3.2 (m, 2H), 2.0 (m, 2H), 1.9 (m, 1H), 1.7 (m, 1H), 1.1 (d, J=6.5 Hz, 6H); LC/MS (ESI+): 526 (M+H).