C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:13]=[C:14]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[O:29])=[CH:24][N:23]=3)[C:15]3[N:16]([N:18]=[CH:19][N:20]=3)[CH:17]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:36]1[N:45]=[CH:44][C:43]2[C:38](=[C:39]([F:50])[CH:40]=[C:41]([C:46]([CH3:49])([CH3:48])[CH3:47])[CH:42]=2)[C:37]1=[O:51])(=O)C.[OH-].[Na+]>C1COCC1.C([O-])(O)=O.[Na+].C(Cl)Cl>[C:46]([C:41]1[CH:42]=[C:43]2[C:38](=[C:39]([F:50])[CH:40]=1)[C:37](=[O:51])[N:36]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:13]=[C:14]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]([N:30]5[CH2:31][CH2:32][O:33][CH2:34][CH2:35]5)=[O:29])=[CH:24][N:23]=4)[C:15]4[N:16]([N:18]=[CH:19][N:20]=4)[CH:17]=3)[C:6]=1[CH2:5][OH:4])[N:45]=[CH:44]2)([CH3:49])([CH3:47])[CH3:48]To a solution of 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(8-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)benzyl acetate (289 mg, 418 μmol, Eq: 1.00) in THF (5.0 ml) was added NaOH (1.0 N, 5.0 ml, 5.00 mmol, Eq: 12.0). The solution was heated to 60° C. for 18 h. The reaction was cooled to room temperature. The reaction was diluted with sat NaHCO3 (aq) and DCM. The layers were separated. The aqueous layer was extracted three times with DCM, and then dried over MgSO4. The solid was removed by filtration. The filtrate was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 0% to 10% MeOH/DCM gradient) to give a residue. The residue was triturated with Et2O to give 6-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{8-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-phenyl)-2H-phthalazin-1-one (61 mg, 23%). 1H NMR (300 MHz, CHLOROFORM-d) d ppm 1.36-1.49 (m, 9H) 3.51-3.95 (m, 8H) 4.40 (s, 2H) 7.20 (dd, J=18.13, 7.18 Hz, 1H) 7.41-7.67 (m, 6H) 7.76 (dd, J=8.31, 2.27 Hz, 1H) 8.31 (d, J=2.64 Hz, 1H) 8.36-8.48 (m, 2H) 8.66 (s, 1H) 8.95 (s, 1H) LC/MS-ESI observed [M+H]+ 649.
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