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

HRID 407673Notes

Reaction equation

HRID 407673 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:27]2[N:36]=[CH:35][C:34]3[C:29](=[C:30]([F:41])[CH:31]=[C:32]([C:37]([CH3:40])([CH3:39])[CH3:38])[CH:33]=3)[C:28]2=[O:42])=[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])[NH:21][N:20]=2)[C:15](=[O:25])[N:14]([CH3:26])[CH:13]=1)(=O)C.[OH-].[Li+]>C1COCC1.C(O)(C)C.O>[C:37]([C:32]1[CH:33]=[C:34]2[C:29](=[C:30]([F:41])[CH:31]=1)[C:28](=[O:42])[N:27]([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])[NH:21][N:20]=4)[C:15](=[O:25])[N:14]([CH3:26])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:36]=[CH:35]2)([CH3:40])([CH3:38])[CH3:39]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86683957(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 866839586-tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methyl-1H-pyrazol-3-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-oneYield 30.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 121a (86 mg, 0.15 mmol) and lithium hydroxide (36 mg, 1.5 mmol) in THF/i-propanol (5:3, 8 mL) and water (2 mL) was stirred at 30° C. for 1 h. The mixture was evaporated under reduced pressure 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 121 (24 mg, 30%) as a white solid. MS-ESI: [M+H]+ 530.3. 1H NMR (500 MHz, CDCl3) δ 8.65 (d, J=5.0 Hz, 1H), 8.35 (d, J=2.0 Hz, 1H), 8.04 (d, J=2.5 Hz, 1H), 7.58-7.53 (m, 4H), 7.44 (s, 1H), 5.78 (s, 1H), 4.51-4.49 (m, 2H), 3.73 (s, 3H), 2.03 (s, 3H), 1.45 (s, 9H).

Workup

  1. customThe mixture was evaporated under reduced pressure
  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-7fafbfbbb7134b79b1ba119564b8bdbe
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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