[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]#[C:15][C:16]2[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([CH:33]4[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:34]4)=[CH:29][CH:28]=3)[N:17]=2)[CH2:7][CH2:6]1)=[O:4].CCN(CC)CC.[H][H]>CN(C=O)C.CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH2:14][CH2:15][C:16]2[C:21]([C:22]([F:23])([F:25])[F:24])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([CH:33]4[CH2:34][N:35]([C:37]([O:39][C:40]([CH3:42])([CH3:43])[CH3:41])=[O:38])[CH2:36]4)=[CH:29][CH:28]=3)[N:17]=2)[CH2:6][CH2:7]1)=[O:4]A suspension of 10% Pd/C (200 mg), tert-butyl 3-(4-((4-((2-(1-(methoxycarbonyl)cyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate (A7) (353 mg, 0.596 mmol) and Et3N (1.5 mL) in DMF (10 mL) was stirred with under a hydrogen atmosphere for 16 hours. The resulting mixture was diluted with EtOAc (60 mL), filtered through Celite and the volatiles were removed under reduced pressure. The residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.) to give the title compound A8 as yellow oil (353 mg, 99%); 1H NMR (400 MHz, d6-DMSO) δ 10.22 (s, 1H), 8.69 (s, 1H), 7.74 (d, J=8.6 Hz, 2H), 7.32-7.26 (m, 5H), 7.22-7.16 (m, 1H), 4.24 (t, J=7.4 Hz, 2H), 3.87-3.71 (m, 3H), 3.49 (s, 3H), 3.17-2.98 (m, 4H), 1.58 (d, J=3.3 Hz, 2H), 1.40 (s, 9H), 1.19 (s, 2H). LCMS-A: rt 6.650 min; m/z 595 [M−H]−.
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