Phenol → 4-(4-Fluorophenyl)-1,2-dimethyl-5-(2-phenoxypyrimidin-4-yl)-1,2-dihydropyrazol-3-one

HRID 1838875Notes

Reaction equation

HRID 1838875 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:18](=[O:34])[N:19]([CH3:33])[N:20]([CH3:32])[C:21]=2[C:22]2[CH:27]=[CH:26][N:25]=[C:24](S(C)(=O)=O)[N:23]=2)=[CH:13][CH:12]=1>C1COCC1>[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:18](=[O:34])[N:19]([CH3:33])[N:20]([CH3:32])[C:21]=2[C:22]2[CH:27]=[CH:26][N:25]=[C:24]([O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:23]=2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 23449924HCID 23449924, compound

Product 1

HCID 101504294-(4-Fluorophenyl)-1,2-dimethyl-5-(2-phenoxypyrimidin-4-yl)-1,2-dihydropyrazol-3-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of phenol (0.12 g, 1.29 mmol) in THF (5 mL) is added sodium hydride (0.04 g, 1.08 mmol). After stirring at room temperature for 10 min, a solution of 4-(4-fluorophenyl)-1,2-dimethyl-5-(2-methanesulfonyl-pyrimidin-4-yl)-1,2-dihydropyrazol-3-one, 30, (0.20 g, 0.55 mmol) in THF (5 mL) is added to the reaction mixture. The mixture is stirred at room temperature for 4 hours. The reaction is then quenched with H2O and diluted with EtOAc. The organic phase is washed with 1N NaOH (×2), dried (MgSO4), filtered and concentrated in vacuo. The crude residue is purified by preparatory HPLC to the desired product: 1H NMR (300 MHz, CDCl3) δ 8.51 (d, J=4.8 Hz, 1H), 7.48 (t, J=8.1 Hz, 2H), 7.36-7.31 (m, 3H), 7.24 (dd, J=7.5, 1.2 Hz, 2H), 7.04 (t, J=9.0 Hz, 2H), 6.94 (d, J=5.1 Hz, 1H), 3.53 (s, 3H), 3.38 (s, 3H); HRMS calcd for C21H18FN4O2 (M+H)+377.1418; found 377.1397.

Workup

  1. stirringThe mixture is stirred at room temperature for 4 hours
  2. customThe reaction is then quenched with H2O
  3. additiondiluted with EtOAc
  4. washThe organic phase is washed with 1N NaOH (×2)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue is purified by preparatory HPLC to the desired product

Sources & evidence

ORD record
ord-b23cfcff88884eaeb747d4a0cc609b56
Source dataset
uspto-grants-2004_01
Patent number
US06677337B2

Reaction notes

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