Potassium Carbonate → N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-c]pyrimidin-7-amine

HRID 1296704Notes

Reaction equation

HRID 1296704 reaction equation
[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[C:15]([C:16](=O)[CH:17]=[CH:18]N(C)C)=[C:11]3[CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH:31]1([NH:36][C:37]([NH2:39])=[NH:38])[CH2:35][CH2:34][CH2:33][CH2:32]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH:31]1([NH:36][C:37]2[N:39]3[N:13]=[C:14]([C:23]4[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=4)[C:15]([C:11]4[CH:10]=[CH:9][N:8]=[C:7]([NH:6][CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[N:12]=4)=[C:16]3[CH:17]=[CH:18][N:38]=2)[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 694496111-[7-(Cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-c]pyrimidin-3-yl]-3-(dimethylamino)prop-2-en-1-oneHCID 178479367HCID 178479367, compound2×

Product 1

HCID 10127619N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-c]pyrimidin-7-amineYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 1-[7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-c]pyrimidin-3-yl]-3-(dimethylamino)prop-2-en-1-one (160 mg, 0.41 mmol) in N,N-dimethylformamide (10 mL) was added N-cyclopentylguanidine hydrochloride (130 mg, 0.82 mmol). Freshly ground anhydrous potassium carbonate (56 mg, 0.41 mmol) was added and the reaction heated to 140° C. for 4 hours. Additional freshly ground anhydrous potassium carbonate (120 mg, 0.87 mmol) and N-cyclopentylguanidine hydrochloride (75 mg, 0.46 mmol) were added and the reaction heated for additional 3 hours. The reaction was allowed to cool and was stirred at room temperature for 16 hours. The mixture was quenched with water, extracted with ethyl acetate (2×), washed with brine, concentrated, and the residue purified by silica chromatography eluting with 5% acetone in dichloromethane to yield 140 mg (75%) of N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-c]pyrimidin-7-amine. 1H NMR (CDCl3): δ 8.09 (d, 1H), 7.80 (d, 1H), 7.66 (dd, 2H), 7.54 (d, 1H), 7.19 (t, 2H), 6.42 (d, 1H), 6.30 (d, 1H), 5.14 (d, 1H), 4.57 (m, 1H), 4.34 (m, 1H), 2.22 (m, 2H), 2.09 (m, 2H), 1.52–1.89 (m, 12H).

Workup

  1. temperaturethe reaction heated for additional 3 hours
  2. temperatureto cool
  3. customThe mixture was quenched with water
  4. extractionextracted with ethyl acetate (2×)
  5. washwashed with brine
  6. concentrationconcentrated
  7. customthe residue purified by silica chromatography
  8. washeluting with 5% acetone in dichloromethane

Sources & evidence

ORD record
ord-d688d84a1f0a477da0a6ff32fe5e41b3
Source dataset
uspto-grants-2007_07
Patent number
US07247626B2

Reaction notes

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