Cesium carbonate → N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(2-cyanoethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 529779Notes

Reaction equation

HRID 529779 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH:26]([F:28])[F:27])=[C:6]([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:7]=1.Br[CH2:30][CH2:31][C:32]#[N:33].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH:26]([F:28])[F:27])=[C:6]([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]([CH2:30][CH2:31][C:32]#[N:33])[N:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 170203-BromopropionitrileHCID 178522413HCID 178522413, compound

Product 1

HCID 118522650N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(2-cyanoethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (500 mg, 1.24 mmol), 3-bromopropanenitrile (412 mg, 3.08 mmol), Cs2CO3 (1.21 g, 3.70 mol) in N,N-dimethylformamide (15 mL) was purged with a gentle flow of nitrogen gas. The resulting mixture was stirred in a sealed tube at 65° C. for 16 then poured into water (200 mL). The crude product was collected by filtration and then purified by flash chromatography on silica eluting with ethyl acetate/petroleum ether (1:2). Appropriate fractions were collected and evaporated to afford N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(2-cyanoethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a light yellow solid (320 mg, 57%). LCMS (Method 17) [M+H]+=458.1, RT=1.67 min.

Workup

  1. customwas purged with a gentle flow of nitrogen gas
  2. additionthen poured into water (200 mL)
  3. filtrationThe crude product was collected by filtration
  4. custompurified by flash chromatography on silica eluting with ethyl acetate/petroleum ether (1:2)
  5. customAppropriate fractions were collected
  6. customevaporated

Sources & evidence

ORD record
ord-8bd7129dd7e740a7823eed2543a4eae2
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

Loading…