Sodium Carbonate → Methyl-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxylate

HRID 1842606Notes

Reaction equation

HRID 1842606 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([O:11][CH:12]([F:14])[F:13])[CH:8]=[N:7][C:6]=12.[CH3:15][O:16][C:17]([C:19]1[S:20][C:21]([CH3:33])=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:23]=1)=[O:18].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[CH3:15][O:16][C:17]([C:19]1[S:20][C:21]([CH3:33])=[C:22]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[C:9]([O:11][CH:12]([F:14])[F:13])[CH:8]=[N:7][C:6]=23)[CH:23]=1)=[O:18]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 46703107Methyl 5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylateHCID 673254323-Bromo-6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidine

Product 1

HCID 68304950Methyl-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxylateYield 66.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a flask containing DMF (40.6 mL) was added 3-bromo-6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidine (1.07 g, 4.06 mmol), methyl-5-methyl-4-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)-thiophene-2-carboxylate (1.20 g, 4.27 mmol), palladium tetrakis (235 mg, 0.203 mmol), and 2 M sodium carbonate (aq) (6.10 mL, 12.2 mmol). The reaction mixture was sealed and degassed with N2 for 5 min. The reaction mixture was then heated to 85° C. for 16 h. The reaction mixture was cooled to room temperature and diluted with dichloromethane. The organic layer was washed twice with saturated sodium bicarbonate (aq) twice and once with brine. The organic layer was dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (0-80% EtOAc/Hex) to afford the title compound (0.916 g, 2.70 mmol). LRMS (APCI) calc'd for (C14H11F2N3O3S) [M+H]+, 340.1; found 340.0.

Workup

  1. customThe reaction mixture was sealed
  2. customdegassed with N2 for 5 min
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with dichloromethane
  5. washThe organic layer was washed twice with saturated sodium bicarbonate (aq) twice
  6. dry with materialThe organic layer was dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography (0-80% EtOAc/Hex)

Sources & evidence

ORD record
ord-45802d7861a34d31931839b18a0970fc
Source dataset
uspto-grants-2015_02
Patent number
US08946237B2

Reaction notes

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