Pivalic acid → HCID 89995597, compound

HRID 1480865Notes

Reaction equation

HRID 1480865 reaction equation
Br[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([NH2:10])=[CH:4][CH:3]=1.[CH3:11][N:12]1[CH:16]=[CH:15][N:14]=[C:13]1[CH3:17].C(O)(=O)C(C)(C)C.F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:11][N:12]1[C:16]([C:2]2[N:7]=[C:6]([O:8][CH3:9])[C:5]([NH2:10])=[CH:4][CH:3]=2)=[CH:15][N:14]=[C:13]1[CH3:17]

Participants

9

Reactant 5

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 156171,2-DimethylimidazoleHCID 105361376-Bromo-2-methoxypyridin-3-amineHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborate

Product 1

HCID 89995597HCID 89995597, compoundYield 35%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

Palladium acetate (5.5 mg, 0.025 mmol) was added to a solution of 6-bromo-2-methoxypyridin-3-amine (25 mg, 0.123 mmol), 1,2-dimethyl-1H-imidazole (35.5 mg, 0.369 mmol), pivalic acid (3.8 mg, 0.037 mmol), tricyclohexylphosphine tetrafluoroborate salt (18.1 mg, 0.049 mmol) and potassium carbonate (25.5 mg, 0.185 mmol) in DMA (410 μL). The reaction mixture was heated under microwave irradiation at 120° C. for 1 hour. The reaction was diluted with EtOAc and quenched with water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The crude mixture was purified by Biotage silica gel column chromatography eluting with 1 to 5% MeOH/aq. NH3 (10/1) in DCM to afford the title compound as a white solid (9 mg, 35%).

Workup

  1. customquenched with water
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude mixture was purified by Biotage silica gel column chromatography
  8. washeluting with 1 to 5% MeOH/aq

Sources & evidence

ORD record
ord-a5794beed83143719ab4496183baf3f3
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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