Sodium Carbonate → N-{4-[2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]pyridin-2-yl}acetamide

HRID 570141Notes

Reaction equation

HRID 570141 reaction equation
Br[C:2]1[C:3]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[N:7][C:6]=12.CC1(C)C(C)(C)OB([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:33](=[O:35])[CH3:34])[CH:27]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2]>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:3]2[C:2]([C:26]3[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:33](=[O:35])[CH3:34])[CH:27]=3)=[C:6]3[N:7]=[CH:8][CH:9]=[CH:10][N:5]3[N:4]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 49760417N-(4-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamideHCID 837474383-Bromo-2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine

Product 1

HCID 90387180N-{4-[2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]pyridin-2-yl}acetamideYield 17%

Reagents, catalysts & solvents 2

HCID 11556747Bis(tricyclohexylphosphine)palladium(II) DichlorideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

3-Bromo-2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine (150 mg, 0.51 mmol) and N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide (148 mg, 0.56 mmol, 1.1 eq) are dissolved in 1.5 mL 1,4-dioxan. To this mixture, bis(tricyclohexylphosphine)palladium(II)-dichloride (57 mg, 0.07 mmol, 0.15 eq) and 0.83 mL sodium carbonate solution (2 molar) are added. The reaction mixture is flushed with argon for 5 mins and then sealed. Next the mixture is heated for 30 min at 150° C. in the microwave (Biotage). The reaction mixture is then poured in water and extracted with dichloromethane (3×20 mL). The organic layer is dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The crude material is purified by column chromatography using silica gel in heptane and ethyl acetate (1:0 to 1:1) as eluent and 0.03 g (17%) of N-{4-[2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]pyridin-2-yl}acetamide are obtained as a white solid.

Workup

  1. customThe reaction mixture is flushed with argon for 5 mins
  2. customsealed
  3. additionThe reaction mixture is then poured in water
  4. extractionextracted with dichloromethane (3×20 mL)
  5. dry with materialThe organic layer is dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material is purified by column chromatography

Sources & evidence

ORD record
ord-6fb2e7e00eaa4498aabd96ebb2001015
Source dataset
uspto-grants-2015_05
Patent number
US09023844B2

Reaction notes

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