Methyl iodide → N-(5-(2,5-dimethylphenyl)-1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1466559Notes

Reaction equation

HRID 1466559 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[C:13]([NH:14][C:15]([C:17]2[CH:18]=[N:19][N:20]3[CH:25]=[CH:24][CH:23]=[N:22][C:21]=23)=[O:16])=[CH:12][NH:11][N:10]=1.IC.[C:28](=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[N:10]([CH3:28])[N:11]=[CH:12][C:13]=1[NH:14][C:15]([C:17]1[CH:18]=[N:19][N:20]2[CH:25]=[CH:24][CH:23]=[N:22][C:21]=12)=[O:16]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 178424880HCID 178424880, compound

Product 1

HCID 66850868N-(5-(2,5-dimethylphenyl)-1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of N-(3-(2,5-dimethylphenyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (0.255 g, 0.767 mmol, 1 eq) in 10 mL N,N-dimethylformamide is added iodomethane (60.0 μL, 0.964 mmol, 1.26 eq) and cesium carbonate (0.562 g, 1.72 mmol, 2.25 eq). The reaction mixture is stirred at 40° C. for 2.5 hours. The reaction mixture was partitioned between ethyl acetate and water, and the organic portion washed with brine, dried over magnesium sulfate, and concentrated. The mixture of regioisomeric products was separated and purified by flash chromatography on silica gel (20 to 90% ethyl acetate in dichloromethane) to yield: 84.3 mg (32%) of N-(3-(2,5-dimethylphenyl)-1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. LCMS (ESI) m+H=347.1; 1H NMR (400 MHz, DMSO-d6) δ: 9.65 (s, 1H), 9.30 (d, 1H), 8.65 (s, 1H), 8.47 (d, 1H), 8.27 (s, 1H), 7.27 (d, 1H), 7.23-7.19 (m, 3H), 3.91 (s, 3H), 2.33 (s, 3H), 2.25 (s, 3H), and 81.8 mg (31%) of N-(5-(2,5-dimethylphenyl)-1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. LCMS (ESI) m+H=347.1; 1H NMR (400 MHz, DMSO-d6) δ: 9.42 (s, 1H), 9.30 (d, 1H), 8.61 (s, 1H), 8.43 (d, 1H), 8.01 (s, 1H), 7.36 (d, 1H), 7.30 (d, 1H) 7.20 (m, 2H), 3.62 (s, 3H), 2.35 (s, 3H), 2.12 (s, 3H).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washthe organic portion washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. additionThe mixture of regioisomeric products
  6. customwas separated
  7. custompurified by flash chromatography on silica gel (20 to 90% ethyl acetate in dichloromethane) to yield: 84.3 mg (32%) of N-(3-(2,5-dimethylphenyl)-1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Sources & evidence

ORD record
ord-11bcff2d7e954130a4dafef0ee8ad8ab
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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