Dimethylformamide → HCID 66851307, compound

HRID 1466573Notes

Reaction equation

HRID 1466573 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:24]=C4N=CC=CN4N=3)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:25][C:26]1([O:29][CH2:28]1)[CH3:27].C(=O)([O-])[O-].[Cs+].[Cs+].C[N:37]([CH3:40])[CH:38]=O>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:24]=[N:10][N:9]4[CH:8]=[CH:4][CH:40]=[N:37][C:38]=34)=[O:15])=[CH:11][N:10]([CH2:25][C:26]([OH:29])([CH3:28])[CH3:27])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 11208Isobutylene oxideHCID 178522410HCID 178522410, compound

Product 1

HCID 66851307HCID 66851307, compoundYield 46%

Conditions

Temperature
50 °C

Procedure

N-(3-(3-chlorophenyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-carboxamide (58.9 mg, 0.174 mmol, 1 eq) was dissolved in 5 mL N,N-dimethylformamide. To this solution was added isobutylene oxide (0.5 mL, 6 mmol, 30 eq) and cesium carbonate (56.4 mg, 0.173 mmol, 1.0 eq). The reaction mixture was stirred at 50° C. for 7.5 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 crude product was purified by reverse phase HPLC and lyophilized to give 33.1 mg (46%) of N-(3-(3-chlorophenyl)-1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. LCMS (ESI) m+H=411.1; 1H NMR (400 MHz, DMSO-d6) δ: 10.02 (s, 1H), 9.36 (d, 1H), 8.83 (d, 1H), 8.69 (s, 1H), 8.35 (s, 1H), 7.84 (s, 1H), 7.76 (d, 1H), 7.58 (t, 1H), 7.49 (d, 1H), 7.33 (d of d, 1H), 4.73 (s, 1H), 4.09 (s, 2H), 1.13 (s, 6H).

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. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-63d66295ee3f417bbcffefd9d5de30ce
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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