Water → 6-Tert-butyl-2-[4-[5-[(1,5-dimethylpyrazol-3-yl)amino]-1-methyl-6-oxo-pyridazin-3-yl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one

HRID 1185114Notes

Reaction equation

C([O:4][CH2:5][C:6]1[C:7]([N:28]2[N:37]=[CH:36][C:35]3[C:30](=[C:31]([F:42])[CH:32]=[C:33]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:34]=3)[C:29]2=[O:43])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[N:21]([CH3:25])[N:20]=2)[C:15](=[O:26])[N:14]([CH3:27])[N:13]=1)(=O)C.O.[OH-].[Li+]>CC(O)C.O1CCCC1>[C:38]([C:33]1[CH:34]=[C:35]2[C:30](=[C:31]([F:42])[CH:32]=1)[C:29](=[O:43])[N:28]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:23]=[C:22]([CH3:24])[N:21]([CH3:25])[N:20]=4)[C:15](=[O:26])[N:14]([CH3:27])[N:13]=3)[CH:10]=[CH:9][N:8]=1)[N:37]=[CH:36]2)([CH3:41])([CH3:39])[CH3:40]

Participants

Conditions

Temperature: 30 °C

Procedure

To a solution of 127c (176 mg, 0.30 mmol) in propan-2-ol (4 mL), tetrahydrofuran (4 mL), and water (1.0 mL) was added lithium hydroxide (72 mg, 3.0 mmol). The mixture was stirred at 30° C. for 2 h. It was then evaporated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 127 (30 mg, 18%) as a white solid. MS-ESI: [M+H]+ 544.8. 1H NMR (500 MHz, MeOD) δ 8.66 (d, J=5.0 Hz, 1H), 8.51 (d, J=2.5 Hz, 1H), 7.88 (s, 1H), 7.88 (s, 1H), 7.76-7.72 (m, 2H), 5.97 (s, 1H), 4.68 (s, 2H), 3.89 (s, 3H), 3.75 (s, 3H), 2.29 (s, 3H), 1.47 (s, 9H)

Workup

customIt was then evaporated under reduced pressure
customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record: ord-b25a37782a1d4cb2889c9c393c0c47eb
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669251B2

Reaction notes

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