Phenolate Sodium → 2-(4-fluorophenyl)-6-hydroxy-3-(2-phenoxypyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

HRID 2052876

Reaction equation

HRID 2052876 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:33])[N:10]3[CH2:25][CH:24]([O:26]C(=O)C(C)(C)C)[CH2:23][N:11]3[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15](S(C)(=O)=O)[N:14]=2)=[CH:4][CH:3]=1.[C:34]1([O-:40])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:33])[N:10]3[CH2:25][CH:24]([OH:26])[CH2:23][N:11]3[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([O:40][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:14]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 4445035Phenolate SodiumHCID 207247412,2-dimethyl-propionic acid 6-(4-fluorophenyl)-7-(2-methane-sulfonyl-pyrimidin-4-y)-5-oxo-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester

Product 1

HCID 102725602-(4-fluorophenyl)-6-hydroxy-3-(2-phenoxypyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-oneYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2,2-dimethyl-propionic acid 6-(4-fluorophenyl)-7-(2-methane-sulfonyl-pyrimidin-4-y)-5-oxo-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester, 35, (50 mg, 0.105 mmol) in THF (1 mL) is slowly cannulated into a solution of sodium phenolate in THF (1 mL) at 0° C. The cooling bath is removed and the reaction stirred at room temperature for 1 hour. The reaction is quenched with NH4Cl (sat. aq.) (500 μL). The reaction mixture is concentrated in vacuo and the residue diluted taken up in ethyl acetate (15 mL). The solution is washed with water (20 mL) and a 5% aqueous Na2CO3 (20 mL). The combined aqueous layers are extracted with ethyl acetate (25 mL) and brine (20 mL), dried, filtered and concentrated in vacuo. The crude material is purified over silica (100% ethyl acetate to 5% to 10% to 20% methyl alcohol/ethyl acetate) to afford 9 mg (21% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.43 (d, J=5.2 Hz, 1H), 7.46 (t, J=7.8 Hz, 2H), 7.31-7.27 (m, 3H), 7.19 (d, J=8.2 Hz, 2H), 7.03 (t, J=8.6 Hz, 2H), 6.80 (d, J=5.2 Hz, 1H), 5.41 (br s, 1H), 4.82 (m, 1H), 4.23 (d, J=12.4 Hz, 1H), 3.95-3.85 (m, 2H), 3.76 (dd, J=12.4, 4.4 Hz, 1H); HRMS m/z calcd for C22H18FN4O3 (MH+) 405.1363, found 405.1365.

Workup

  1. customThe cooling bath is removed
  2. customThe reaction is quenched with NH4Cl (sat. aq.) (500 μL)
  3. concentrationThe reaction mixture is concentrated in vacuo
  4. additionthe residue diluted
  5. washThe solution is washed with water (20 mL)
  6. extractionThe combined aqueous layers are extracted with ethyl acetate (25 mL) and brine (20 mL)
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material is purified over silica (100% ethyl acetate to 5% to 10% to 20% methyl alcohol/ethyl acetate)

Sources & evidence

ORD record
ord-4278682713eb47d1a89591222ba77583
Source dataset
uspto-grants-2008_02
Patent number
US07326714B2

Linked notes

Loading…