C(O[C:6](=[O:45])[NH:7][CH2:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[CH:21]=[C:20]([NH:22][C:23]([C:25]3[CH:26]=[N:27][N:28]4[CH:33]=[CH:32][CH:31]=[N:30][C:29]=34)=[O:24])[C:19]([C:34]3[CH:39]=[C:38]([Cl:40])[CH:37]=[CH:36][C:35]=3[O:41][CH:42]([F:44])[F:43])=[N:18]2)[CH2:13][CH2:12]1)(C)(C)C.[C:46](O)(C(F)(F)F)=O.C(Cl)(=O)C>C(Cl)Cl.N1C=CC=CC=1>[ClH:40].[C:6]([NH:7][CH2:8][CH2:9][CH2:10][N:11]1[CH2:12][CH2:13][CH:14]([N:17]2[CH:21]=[C:20]([NH:22][C:23]([C:25]3[CH:26]=[N:27][N:28]4[CH:33]=[CH:32][CH:31]=[N:30][C:29]=34)=[O:24])[C:19]([C:34]3[CH:39]=[C:38]([Cl:40])[CH:37]=[CH:36][C:35]=3[O:41][CH:42]([F:43])[F:44])=[N:18]2)[CH2:15][CH2:16]1)(=[O:45])[CH3:46][3-(4-{3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidin-1-yl)propyl]carbamic acid tert-butyl ester (129 mg, 0.20 mmol) was dissolved in DCM (2 mL) and TFA (2 mL) was added. The reaction was stirred at room temperature for 1 hour and then evaporated to dryness. The residue was dissolved in MeOH and loaded onto an SCX-2 cartridge which had been conditioned with MeOH. After flushing with MeOH, the product was eluted with 2M ammonia in MeOH. Evaporation of the basic fractions gave a residue which was dissolved in pyridine (2 mL). Acetyl chloride (21 μL, 0.30 mmol) was added and the solution was allowed to stand at room temperature for 5 days. The volatiles were evaporated and azeotroped with toluene. The residue was dissolved in MeOH and loaded onto an SCX-2 cartridge which had been conditioned with MeOH. After flushing with MeOH, the product was eluted with 2M ammonia in MeOH. Evaporation gave a glassy solid which was purified by HPLC (Method 3). The pure amine was dissolved in MeOH and 1.25M methanolic HCl was added. The volatiles were evaporated and the solid product was triturated with EtOAc/Et2O to give the title compound as a white solid (40 mg, 32%). LCMS (Method 5) [M+H]+=587.0, RT=2.91 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.89 (s, 1H), 9.76 (s, 1H), 9.35 (dd, 1H, J=1.5, 7.0 Hz), 8.69 (dd, 1H, J=1.6, 4.2 Hz), 8.67 (s, 1H), 8.39 (s, 1H), 8.04 (t, 1H, J=5.8 Hz), 7.67-7.61 (m, 2H), 7.46 (d, 2H, J=8.4 Hz), 7.31 (dd, 1H, J=4.2, 6.9 Hz), 7.26 (t, 1H, J=73.4 Hz), 4.64-4.54 (m, 1H), 3.64 (d, 2H, J=12.2 Hz), 3.21-3.01 (m, 6H), 2.40-2.29 (m, 4H), 1.84 (m, 5H).
불러오는 중…