Cesium carbonate → 7-Cyclohexyl-6-[4-(3-trifluoromethyl-benzyloxy)-phenyl]-pyrazolo[1,5-a]pyrimidine-3-carbonitrile

HRID 270945Notes

Reaction equation

HRID 270945 reaction equation
[CH:1]1([C:7]2[N:12]3[N:13]=[CH:14][C:15]([C:16]#[N:17])=[C:11]3[N:10]=[CH:9][C:8]=2[C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:31][C:32]([F:42])([F:41])[C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][CH:40]=1)[CH2:36]Br>CN(C)C=O.O>[CH:1]1([C:7]2[N:12]3[N:13]=[CH:14][C:15]([C:16]#[N:17])=[C:11]3[N:10]=[CH:9][C:8]=2[C:18]2[CH:19]=[CH:20][C:21]([O:24][CH2:36][C:35]3[CH:38]=[CH:39][CH:40]=[C:33]([C:32]([F:31])([F:41])[F:42])[CH:34]=3)=[CH:22][CH:23]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 1230611-(Bromomethyl)-3-(trifluoromethyl)benzeneHCID 159580147-Cyclohexyl-6-(4-hydroxyphenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile

Product 1

HCID 184458837-Cyclohexyl-6-[4-(3-trifluoromethyl-benzyloxy)-phenyl]-pyrazolo[1,5-a]pyrimidine-3-carbonitrileYield 80.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 53 mg (0.17 mmol) of 7-cyclohexyl-6-(4-hydroxy-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carbonitrile in 3 mL of dimethylformamide (DMF) was added 72 mg (0.22 mmol) of cesium carbonate (Cs2CO3), followed by 0.034 mL (0.22 mmol) of 3-(trifluoromethyl)-benzyl bromide, and the resulting heterogeneous mixture was stirred at rt overnight. The reaction mixture was diluted with water and extracted with ethyl acetate, and the combined organic extracts were concentrated to give a residue which was chromatographed on silica gel (Biotage; DCM) to afford 65 mg (80% yield) of desired 7-cyclohexyl-6-[4-(3-trifluoromethyl-benzyloxy)-phenyl]-pyrazolo[1,5-a]pyrimidine-3-carbonitrile as indicated by 1H NMR; LC-MS—calcd for C27H23F3N4O [M++H]+: 477.18, found: 477.1.

Workup

  1. extractionextracted with ethyl acetate
  2. concentrationthe combined organic extracts were concentrated
  3. customto give a residue which
  4. customwas chromatographed on silica gel (Biotage; DCM)

Sources & evidence

ORD record
ord-c7386ca99c4c4ff685cb9af1ca05bb12
Source dataset
uspto-grants-2008_11
Patent number
US07449488B2

Reaction notes

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