Potassium Carbonate → HCID 58042459, compound

HRID 2048111Notes

Reaction equation

HRID 2048111 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:17]=[C:18]([NH2:32])[CH:19]=[N:20][C:21]=1[O:22][CH:23]([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25].C(=O)([O-])[O-].[K+].[K+].CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C>C(O)(C)(C)C.CC([O-])=O.CC([O-])=O.[Pd+2].O.C(OCC)(=O)C>[Cl:15][C:16]1[CH:17]=[C:18]([NH:32][C:2]2[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=2)[CH:19]=[N:20][C:21]=1[O:22][CH:23]([C:24]([F:25])([F:26])[F:27])[C:28]([F:31])([F:30])[F:29]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 11334366Tert-butyl 4-bromobenzoateHCID 25112535Brettphos2×HCID 58042501HCID 58042501, compound

Product 1

HCID 58042459HCID 58042459, compoundYield 48.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolvent2×HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a degassed suspension of tert-butyl 4-bromobenzoate (Preparation 257, 250 mg, 0.97 mmol), 5-chloro-6-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)pyridin-3-amine (Preparation 256, 430 mg, 1.46 mmol) and potassium carbonate (403 mg, 2.92 mmol) in a mixture of terbutanol (10 ml)/water (0.2 ml) was added Pd(OAc)2 (1 mol %) and BrettPhos (3 mol %). The mixture was heated at 110° C. for 18 hours. After 18 hours, further portions of Pd(OAc)2 (1 mol %) and BrettPhos (3 mol %) were added and the reaction was heated for 24 hours at 110° C. The reaction was cooled to room temperature, ethyl acetate (50 mL) and water (15 mL) were added, the phases were separated and the combined organics evaporated. The crude product was purified by silica gel column chromatography, eluting with DCM in Heptane (10% to 80%), to give the title compound as an oil (0.22 g, 48%).

Workup

  1. temperaturethe reaction was heated for 24 hours at 110° C
  2. temperatureThe reaction was cooled to room temperature
  3. customthe phases were separated
  4. customThe crude product was purified by silica gel column chromatography
  5. washeluting with DCM in Heptane (10% to 80%)

Sources & evidence

ORD record
ord-69332b8d40644f7ab5af8149eb15681c
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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