Cesium carbonate → 3-(4-Chlorophenyl)-2-(2-chlorophenyl)-7-(2,2,2-trifluoroethoxy)-pyrazolo[1,5-a]pyrimidine

HRID 348034Notes

Reaction equation

HRID 348034 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])=[N:10][N:11]3[C:16]([OH:17])=[CH:15][CH:14]=[N:13][C:12]=23)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[F:31][C:32]([F:43])([F:42])[CH2:33]OS(C(F)(F)F)(=O)=O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])=[N:10][N:11]3[C:16]([O:17][CH2:33][C:32]([F:43])([F:42])[F:31])=[CH:15][CH:14]=[N:13][C:12]=23)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 178516366HCID 178516366, compound

Product 1

HCID 100032343-(4-Chlorophenyl)-2-(2-chlorophenyl)-7-(2,2,2-trifluoroethoxy)-pyrazolo[1,5-a]pyrimidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-(4-chlorophenyl)-2-(2-chlorophenyl)-pyrazolo[1,5-a]pyrimidin-7-ol (I-12A-1a; 65 mg, 0.18 mmol) and Cs2CO3 (59 mg, 0.18 mmol) in DMF (1.5 ml) was added a DMF solution (0.1 ml) of trifluoromethanesulfonic acid 2,2,2-trifluoroethyl ester (42 mg, 0.18 mmol). After stirring at 60° C. overnight, the mixture was extracted from pH 7 water with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and then concentrated, in vacuo, to afford the crude product. Purification on a Chromatotron using 1:0:0, 20:1:0, and then 20:0:1 methylene chloride/ethyl acetate/methanol as eluants afforded, in addition to two N-alkylated isomers, product 12A-1 (16.5 mg, 21%) as a solid: +ESI MS (M+1) 438.4; 1H NMR (400 MHz, CD3OD) δ 8.56 (d, J=5.0 Hz, 1H), 7.55–7.41 (m, 6H), 7.24 (d, J=8.7 Hz, 2H), 6.80 (d, J=5.0 Hz, 1H), 5.16 (q, J=7.9 Hz, 2H).

Workup

  1. extractionthe mixture was extracted from pH 7 water with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated, in vacuo
  5. customto afford the crude product
  6. customPurification on a Chromatotron
  7. custom20:0:1 methylene chloride/ethyl acetate/methanol as eluants afforded, in addition to two N-alkylated isomers, product 12A-1 (16.5 mg, 21%) as a solid

Sources & evidence

ORD record
ord-47cd86927e724e949d798577766f0848
Source dataset
uspto-grants-2007_02
Patent number
US07176210B2

Reaction notes

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