Sodium Carbonate → HCID 89488463, compound

HRID 628463Notes

Reaction equation

HRID 628463 reaction equation
Br[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)=[N:5][N:4]2[CH2:14][CH2:15][CH2:16][C:3]=12.CC1(C)C(C)(C)OB([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:31]C(=O)OC(C)(C)C)[CH:26]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2]>[F:13][C:10]1[CH:11]=[CH:12][C:7]([C:6]2[C:2]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([NH2:31])[CH:26]=3)=[C:3]3[CH2:16][CH2:15][CH2:14][N:4]3[N:5]=2)=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 49760449tert-butyl N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamateHCID 89488335HCID 89488335, compound

Product 1

HCID 89488463HCID 89488463, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

3-bromo-2-(4-fluorophenyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (700 mg, 2.5 mmol) and tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate (727 mg, 2.27 mmol, 1.1 eq) are dissolved in 10 mL 1,4-dioxan. To this mixture is added Bis(tricyclohexylphosphine)palladium(II)-dichloride (168 mg, 0.22 mmol, 0.1 eq) and 5.4 mL sodium carbonate solution (2 molar). The reaction mixture is flushed with argon for 5 mins and then sealed. Next the mixture is heated for 12 mins at 150° C. in the microwave (Biotage). After cooling, insoluble components are filtered off over Celite and the residue washed with 1,4-dioxan. The organic phase is evaporated and the crude product purified by column chromatography over silica gel using dichloromethane/methanol (95:5) as eluent. After evaporation of the solvents 530 mg (72%) of 4-[2-(4-fluorophenyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]pyridin-2-amine are obtained as a colourless solid.

Workup

  1. customThe reaction mixture is flushed with argon for 5 mins
  2. customsealed
  3. temperatureAfter cooling
  4. filtrationinsoluble components are filtered off over Celite
  5. washthe residue washed with 1,4-dioxan
  6. customThe organic phase is evaporated
  7. customthe crude product purified by column chromatography over silica gel
  8. customAfter evaporation of the solvents 530 mg (72%) of 4-[2-(4-fluorophenyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]pyridin-2-amine
  9. customare obtained as a colourless solid

Sources & evidence

ORD record
ord-fa4d73ebf42146b6b4ee92679d21e6c9
Source dataset
uspto-grants-2016_04
Patent number
US09314026B2

Reaction notes

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