Phenol → 1-oxo-3-(2-phenoxy-pyrimidin-4-yl)-6,7-dihydro-1H,5H-pyrazolo[1,2-a]pyrazole-2-carboxylic acid 2-chloro-benzylamide

HRID 1455254Notes

Reaction equation

HRID 1455254 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:39]=[CH:38][CH:37]=[CH:36][C:12]=1[CH2:13][NH:14][C:15]([C:17]1[C:24](=[O:25])[N:20]2[CH2:21][CH2:22][CH2:23][N:19]2[C:18]=1[C:26]1[CH:31]=[CH:30][N:29]=[C:28](S(C)(=O)=O)[N:27]=1)=[O:16]>C1COCC1.C([O-])(O)=O.[Na+]>[Cl:10][C:11]1[CH:39]=[CH:38][CH:37]=[CH:36][C:12]=1[CH2:13][NH:14][C:15]([C:17]1[C:24](=[O:25])[N:20]2[CH2:21][CH2:22][CH2:23][N:19]2[C:18]=1[C:26]1[CH:31]=[CH:30][N:29]=[C:28]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:27]=1)=[O:16]

Participants

6

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 575317923-(2-methanesulfonyl-pyrimidin-4-yl)-1-oxo-6,7-dihydro-1H,5H-pyrazolo[1,2-a]pyrazole-2-carboxylic acid 2-chloro-benzylamide

Product 1

HCID 114085911-oxo-3-(2-phenoxy-pyrimidin-4-yl)-6,7-dihydro-1H,5H-pyrazolo[1,2-a]pyrazole-2-carboxylic acid 2-chloro-benzylamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of phenol (0.09 g, 1.00 mmol) in THF (2 mL) is added sodium hydride (0.05 g of a 60% dispersion in mineral oil, 0.80 mmol). After stirring 5 min at room temperature a solution of 3-(2-methanesulfonyl-pyrimidin-4-yl)-1-oxo-6,7-dihydro-1H,5H-pyrazolo[1,2-a]pyrazole-2-carboxylic acid 2-chloro-benzylamide, 16, (0.18 g, 0.40 mmol) in THF (3 mL) is added to the reaction mixture. After stirring 1.5 h at room temperature, the mixture is diluted with aqueous saturated NaHCO3. The aqueous phase is extracted with CHCl3 (×3). The combined organic phases are washed with aqueous saturated NaHCO3, dried (MgSO4), filtered and concentrated in vacuo. The crude residue is purified over silica (5% MeOH/CHCl3) to afford 110 mg of the desired product as a white solid: 1H NMR (300 MHz, CDCl3) δ 9.59 (bd s, NH), 8.75 (d, J=5.1 Hz, 1H), 8.49 (d, J=7.2 Hz, 1H), 7.49-7.20 (m, 9H), 4.72 (d, J=5.4 Hz, 2H), 4.04 (t, J=7.2 Hz, 2H), 3.98 (t, J=7.2 Hz, 2H), 2.57 (dddd, J=6.9, 6.9, 6.9, 6.9 Hz, 2H); ESI+ MS: m/z (rel intensity) 462.1 (100, M++H); HRMS m/z calcd for C24H20ClN5O3 (M+H+) 462.1333, found 462.1320.

Workup

  1. additionis added to the reaction mixture
  2. extractionThe aqueous phase is extracted with CHCl3 (×3)
  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 (5% MeOH/CHCl3)

Sources & evidence

ORD record
ord-94b4804b2263439180bf5d4884405d13
Source dataset
uspto-grants-2009_01
Patent number
US07482356B2

Reaction notes

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