2-(3,5-Difluorophenyl)ethan-1-amine → [2-(3,5-Difluoro-phenyl)-ethyl]-{4-[3-(2(S)-ethyl-piperazin-1-ylmethyl)-phenyl]-pyrimidin-2-yl}-amine
Reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]3[CH:26]=[CH:25][N:24]=[C:23](Cl)[N:22]=3)[CH:16]=2)[CH:10]([CH2:28][CH3:29])[CH2:9]1)=O)(C)(C)C.[F:30][C:31]1[CH:32]=[C:33]([CH2:38][CH2:39][NH2:40])[CH:34]=[C:35]([F:37])[CH:36]=1>>[F:30][C:31]1[CH:32]=[C:33]([CH2:38][CH2:39][NH:40][C:23]2[N:22]=[C:21]([C:17]3[CH:18]=[CH:19][CH:20]=[C:15]([CH2:14][N:11]4[CH2:12][CH2:13][NH:8][CH2:9][C@@H:10]4[CH2:28][CH3:29])[CH:16]=3)[CH:26]=[CH:25][N:24]=2)[CH:34]=[C:35]([F:37])[CH:36]=1Participants
3
Procedure
Intermediate 112 was coupled with 2-(3,5-difluoro-phenyl)-ethylamine following procedure F. The enantiomers of this product were separated by chiral HPLC, with compound 195 coming from the first peak to elute. The resulting product was deprotected following procedure G2. LC-MS showed the product had the expected M+H+ of 439. 1H NMR (Varian 300 MHz, CD3OD, shifts relative to the solvent peak at 3.3 ppm) δ 8.74 (s, 1H), 8.38 (d, 2H), 7.97 (d, 1H), 7.71 (m, 2H), 7.00 (d, 2H), 6.74 (s, 1H), 4.58 (m, 6H), 4.07 (m, 4H), 3.25 (m, 3H), 3.07 (t, 2H), 1.39 (t, 3H).