Lithium Hydroxide → 6-Tert-butyl-2-[4-[5-[(5-cyclopropyl-1-methyl-pyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one

HRID 407696Notes

Reaction equation

C([O:4][CH2:5][C:6]1[C:7]([N:30]2[N:39]=[CH:38][C:37]3[C:32](=[C:33]([F:44])[CH:34]=[C:35]([C:40]([CH3:43])([CH3:42])[CH3:41])[CH:36]=3)[C:31]2=[O:45])=[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]([CH:24]3[CH2:26][CH2:25]3)[N:21]([CH3:27])[N:20]=2)[C:15](=[O:28])[N:14]([CH3:29])[CH:13]=1)(=O)C.[OH-].[Li+]>C(O)(C)C.C1COCC1.O>[C:40]([C:35]1[CH:36]=[C:37]2[C:32](=[C:33]([F:44])[CH:34]=1)[C:31](=[O:45])[N:30]([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]([CH:24]5[CH2:26][CH2:25]5)[N:21]([CH3:27])[N:20]=4)[C:15](=[O:28])[N:14]([CH3:29])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:39]=[CH:38]2)([CH3:43])([CH3:41])[CH3:42]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 126g (100 mg, 0.16 mmol) and lithium hydroxide (72 mg, 3.0 mmol) in i-propanol/THF (1:1, 4 mL) and water (1 mL) was stirred at 50° C. for 2 h. The mixture was evaporated under reduced pressure. The residue was purified by reverse-phase Combiflash to afford 126 (32 mg, 35%) as a white solid. MS-ESI: [M+H]+ 570.3. 1H NMR (500 MHz, DMSO-d6) δ 8.63 (d, J=5.0 Hz, 1H), 8.33 (d, J=2.0 Hz, 1H), 7.94 (d, J=1.5 Hz, 1H), 7.56-7.55 (m, 2H), 7.53-7.51 (m, 2H), 7.33 (s, 1H), 5.53 (s, 1H) 4.49-4.48 (m, 2H), 4.04-4.02 (m, 1H), 3.79 (s, 3H), 3.69 (s, 3H), 1.69-1.65 (m, 1H), 1.43 (s, 9H), 0.97-0.94 (m, 2H), 0.68-0.65 (m, 2H).

Workup

customThe mixture was evaporated under reduced pressure
customThe residue was purified by reverse-phase Combiflash

Sources & evidence

ORD record: ord-304798d256194026b2d482074d42fb38
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754077B2

Reaction notes

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