Phenol → 2-(2-chlorobenzoyl)-3-(2-phenoxy-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

HRID 1455262Notes

Reaction equation

HRID 1455262 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Cl:10][C:11]1[CH:37]=[CH:36][CH:35]=[CH:34][C:12]=1[C:13]([C:15]1[C:22](=[O:23])[N:18]2[CH2:19][CH2:20][CH2:21][N:17]2[C:16]=1[C:24]1[CH:29]=[CH:28][N:27]=[C:26](S(C)(=O)=O)[N:25]=1)=[O:14]>C1COCC1.C([O-])(O)=O.[Na+]>[Cl:10][C:11]1[CH:37]=[CH:36][CH:35]=[CH:34][C:12]=1[C:13]([C:15]1[C:22](=[O:23])[N:18]2[CH2:19][CH2:20][CH2:21][N:17]2[C:16]=1[C:24]1[CH:29]=[CH:28][N:27]=[C:26]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:25]=1)=[O:14]

Participants

6

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 574381012-(2-chlorobenzoyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

Product 1

HCID 114646442-(2-chlorobenzoyl)-3-(2-phenoxy-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of phenol (0.04 g, 0.43 mmol) in THF (1 mL) is added sodium hydride (0.02 g of a 60% dispersion in mineral oil, 0.32 mmol). After stirring 5 min at room temperature a solution of 2-(2-chloro-benzoyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one, 24, (0.09 g, 0.21 mmol) in THF (2 mL) is added to the reaction mixture. After stirring 1.5 hours at room temperature, the mixture is diluted with aqueous saturated NaHCO3. The aqueous phase is extracted three times with CHCl3 and the combined organic phases are washed with aqueous saturated NaHCO3, dried (MgSO4), filtered and concentrated in vacuo. The crude residue is purified over silica (10% MeOH/CHCl3) to afford 30 mg of the desired product. 1H NMR (300 MHz, CDCl3) δ 8.77 (d, J=5.1 Hz, 1H), 8.04 (d, J=5.1 Hz, 1H), 7.49 (t, J=7.8 Hz, 1H), 7.41-7.20 (m, 9H), 4.00 (t, J=7.2 Hz, 2H), 3.95 (t, J=7.2 Hz, 2H), 2.54 (dddd, J=7.5, 7.5, 7.5, 7.5 Hz, 2H); ESI− MS: m/z (rel intensity) 431.1 (100, M+−H).

Workup

  1. additionis added to the reaction mixture
  2. extractionThe aqueous phase is extracted three times with CHCl3
  3. washthe combined organic phases are washed with aqueous saturated NaHCO3
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue is purified over silica (10% MeOH/CHCl3)

Sources & evidence

ORD record
ord-a8d5aedf7aa546da9b8111f0b1e25d8f
Source dataset
uspto-grants-2009_01
Patent number
US07482356B2

Reaction notes

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