Lithium hydroxide, monohydrate → 6-Tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-6-oxo-5-(pyrazin-2-ylamino)-3-pyridyl]-2-pyridyl]phthalazin-1-one

HRID 1185238Notes

Reaction equation

HRID 1185238 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:24]=[N:23][CH:22]=[CH:21][N:20]=2)[C:15](=[O:25])[N:14]([CH3:26])[CH:13]=1)(=O)C.O.[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:24]=[N:23][CH:22]=[CH: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 168937Lithium hydroxide, monohydrateHCID 86684086(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-6-oxo-5-(pyrazin-2-ylamino)-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 866840876-Tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-6-oxo-5-(pyrazin-2-ylamino)-3-pyridyl]-2-pyridyl]phthalazin-1-oneYield 45.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 160b (120 mg, 0.21 mmol) and lithium hydroxide monohydrate (88 mg, 2.1 mmol) in THF/i-propanol (4:2, 6 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 (10 mL). It was then extracted with ethyl acetate (2×20 mL). The combined ethyl acetate extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 160 (50 mg, 45%) as a white solid. MS-ESI: [M+H]+ 527.8. 1H NMR (500 MHz, CHCl3) δ 8.78 (d, J=2.5 Hz, 1H), 8.71 (d, J=5.0 Hz, 1H), 8.36 (d, J=2.0 Hz, 1H), 8.31 (s, 1H), 8.19 (s, 1H), 8.14 (s, 1H), 8.05 (d, J=2.0 Hz, 1H), 7.81 (d, J=2.5 Hz, 1H), 7.59 (s, 1H), 7.56-7.55 (m, 2H)

Workup

  1. customThe mixture was evaporated under reduced pressure
  2. additionthe residue was diluted with water (10 mL)
  3. extractionIt was then extracted with ethyl acetate (2×20 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-a38d742e5f0e401298d6aef491f389a3
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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