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

HRID 1581517Notes

Reaction equation

HRID 1581517 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:24](=[O:25])[N:20]3[CH2:21][CH2:22][CH2:23][N:19]3[C:18]=2[C:26]2[CH:31]=[CH:30][N:29]=[C:28](S(C)(=O)=O)[N:27]=2)=[CH:13][CH:12]=1>C1COCC1.C([O-])(O)=O.[Na+]>[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:24](=[O:25])[N:20]3[CH2:21][CH2:22][CH2:23][N:19]3[C:18]=2[C:26]2[CH:31]=[CH:30][N:29]=[C:28]([O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:27]=2)=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 129914052-(4-fluorophenyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

Product 1

HCID 102715862-(4-Fluorophenyl)-3-(2-phenoxy-pyrimidin-4-yl)-6,7-dihydro-5h pyrazolo-[1,2-a]pyrazol-1-oneYield 38%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of phenol (0.66 g, 7.08 mmol) in THF (5 mL) is added NaH (0.24 g, 5.91 mmol) followed by a solution of the crude 2-(4-fluorophenyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one, 5, prepared herein above (0.25 g, 0.67 mmol) in THF (2 mL). The reaction mixture is stirred for 1.5 hours at room temperature, diluted with aqueous NaHCO3 and extracted with twice with ethyl acetate. The organic layers are combined, dried over MgSO4, and concentrated in vacuo to afford the crude product which is purified over silica (100% EtOAc, followed by 10% MeOH/EtOAc) to provide 0.35 g (38% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.47 (d, J=5.1 Hz, 1H), 7.49 (dd, J=7.8, 7.8 Hz, 2H), 7.40 (ddd, J=5.4, 5.4 Hz, 2H), 7.35-7.22 (m, 3H), 7.10 (dd, J=8.4, 8.4 Hz, 2H), 6.90 (d, J=6.8 Hz, 1H), 4.05 (t, J=7.2 Hz, 2H), 3.86 (t, J=7.2 Hz, 2H), 2.59 (dt, J=7.2, 7.2 Hz, 2H); HRMS calcd for C22H18FN4O2 (M+H)+ 389.1414; found 389.1407. This compound corresponds to analog 1 from Table I.

Workup

  1. extractionextracted with twice with ethyl acetate
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customto afford the crude product which
  5. customis purified over silica (100% EtOAc, followed by 10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-aa573fcb092c4df190b946b096b325e1
Source dataset
uspto-grants-2004_05
Patent number
US06730668B2

Reaction notes

Loading…