Isopropyl iodide → N-(3-(3-chlorophenyl)-1-isopropyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1466572Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:31](I)([CH3:33])[CH3:32]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH:31]([CH3:33])[CH3:32])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

N-(3-(3-chlorophenyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (68.9 mg, 0.203 mmol, 1 eq) was dissolved in 4 mL N,N-dimethylformamide. To this solution was added cesium carbonate (148 mg, 0.454 mmol, 2.23 eq) and isopropyl iodide (23.0 μL, 0.230 mmol, 1.13 eq). The reaction mixture was stirred at 50° C. for 2 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 crude product was purified by reverse phase HPLC and lyophilized to give 47.2 mg (61%) of N-(3-(3-chlorophenyl)-1-isopropyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. LCMS (ESI) m+H=381.1; 1H NMR (400 MHz, DMSO-d6) δ: 9.99 (s, 1H), 9.37 (d, 1H), 8.85 (d, 1H), 8.70 (s, 1H), 8.36 (s, 1H), 7.85 (s, 1H), 7.77 (d, 1H), 7.57 (t, 1H), 7.48 (d, 1H), 7.34 (d of d, 1H), 4.59 (d of q, 1H), 1.48 (d, 6H).

Workup

customThe reaction mixture was partitioned between ethyl acetate and water
washthe organic portion washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated
customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record: ord-fa08be7ae24f48cf939c6597e99b3b77
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999998B2

Reaction notes

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