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

HRID 1185122Notes

Reaction equation

HRID 1185122 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])[O: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>[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])[O: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

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 86683978(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methylisoxazol-3-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 866839796-Tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methylisoxazol-3-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-oneYield 33%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 129b (280 mg, 0.49 mmol) in THF (4 mL), i-propanol (4 mL), and water (2 mL) was added lithium hydroxide (24 mg, 0.98 mmol). The reaction mixture was stirred at room temperature for 1 h. It was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 129 as a white solid (85 mg, 33%). MS-ESI: [M+H]+ 531.3. 1H NMR (500 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.58 (d, J=5.0 Hz, 1H), 8.54 (d, J=3.0 Hz, 1H), 7.99 (d, J=2.0 Hz, 1H), 7.91 (d, J=1.0 Hz, 1H), 7.78 (dd, J=1.0, 13.0 Hz, 1H), 7.56 (d, J=2.0 Hz, 1H), 7.51 (d, J=5.0 Hz, 1H), 6.26 (s, 1H), 4.92 (s, 1H), 4.43 (d, J=6.0 Hz, 2H), 3.61 (s, 3H), 2.32 (s, 3H), 1.40 (s, 9H).

Workup

  1. concentrationIt was concentrated under reduced pressure
  2. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-e98ea9bd003b4cccb94d101f4f144f55
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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