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

HRID 407668Notes

Reaction equation

HRID 407668 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])[CH:13]=1)(=O)C.[OH-].[Li+]>C(O)(C)C.C1COCC1.O>[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])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:37]=[CH:36]2)([CH3:41])([CH3:39])[CH3:40]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86683951(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 866839526-Tert-butyl-2-[4-[5-[(1,5-dimethylpyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-oneYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 119b (150 mg, 0.26 mmol) and lithium hydroxide (61.4 mg, 2.6 mmol) in i-propanol/THF (1:1, 4 mL) and water (1 mL) was stirred at 30° C. for 1 h. The mixture was evaporated in vacuo and the residue was diluted with water (5 mL). It was then extracted with ethyl acetate (2×10 mL). The combined ethyl acetate extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 119 (75.0 mg, 54%) as a white solid. MS-ESI: [M+H]+ 544.3. 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J=5.0 Hz, 1H), 8.35 (d, J=2.0 Hz, 1H), 7.97 (d, J=2.0 Hz, 1H), 7.59-7.53 (m, 4H), 7.37 (s, 1H), 5.74 (s, 1H), 4.51 (s, 2H), 4.07 (s, 1H), 3.72 (s, 3H), 3.70 (s, 3H), 2.25 (s, 3H), 1.46 (s, 9H).

Workup

  1. customThe mixture was evaporated in vacuo
  2. additionthe residue was diluted with water (5 mL)
  3. extractionIt was then extracted with ethyl acetate (2×10 mL)
  4. extractionThe combined ethyl acetate extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-e2fa695a7e5b43ff83e4ef82d5e4641d
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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