Sodium Carbonate → N-(1-methyl-4-(2-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1466575Notes

Reaction equation

HRID 1466575 reaction equation
Br[C:2]1[C:3]([NH:8][C:9]([C:11]2[CH:12]=[N:13][N:14]3[CH:19]=[CH:18][CH:17]=[N:16][C:15]=23)=[O:10])=[N:4][N:5]([CH3:7])[CH:6]=1.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[CH3:7][N:5]1[CH:6]=[C:2]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[C:21]([F:32])([F:31])[F:20])[C:3]([NH:8][C:9]([C:11]2[CH:12]=[N:13][N:14]3[CH:19]=[CH:18][CH:17]=[N:16][C:15]=23)=[O:10])=[N:4]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 66851236N-(4-bromo-1-methyl-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Product 1

HCID 49856849N-(1-methyl-4-(2-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

To a stir-bar equipped microwave vial was added: N-(4-bromo-1-methyl-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (101 mg, 0.313 mmol, 1 eq), 2-trifluoromethylphenyl boronic acid (126.6 mg, 0.6666 mmol, 2.13 eq), bis(triphenylphosphine)palladium(II) chloride (26.8 mg, 0.0382 mmol, 0.12 eq), sodium carbonate (1.0 mL of a 2.0 M aqueous solution, 2 mmol, 6 eq), and 3 mL acetonitrile. The reaction mixture was subjected to microwave irradiation at 130° C. for 30 minutes. 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 4.7 mg (4%) of N-(1-methyl-4-(2-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. LCMS (ESI) m+H=387.1; 1H NMR (400 MHz, DMSO-d6) δ: 9.58 (s, 1H), 9.32 (d, 1H), 8.74 (d, 1H), 8.57 (s, 1H), 7.78 (s, 1H), 7.74 (d, 1H), 7.60 (t, 1H), 7.49 (m, 2H), 7.28 (d of d, 1H), 3.87 (s, 3H).

Workup

  1. customTo a stir-bar equipped microwave vial
  2. additionwas added
  3. customirradiation at 130° C. for 30 minutes
  4. customThe reaction mixture was partitioned between ethyl acetate and water
  5. washthe organic portion washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-213a512c9e9d4ba78ea665e3e7419b28
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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