Potassium Carbonate → HCID 67375610, compound

HRID 525191Notes

Reaction equation

HRID 525191 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][CH:14]3[CH2:17][N:16]([C:18]([CH:20]4[CH2:22][CH2:21]4)=[O:19])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:23])=[C:4]([F:24])[CH:3]=1.[NH:25]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31](B(O)O)[CH:32]=2)[CH:27]=[CH:26]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C>[CH:20]1([C:18]([N:16]2[CH2:17][CH:14]([CH2:13][C:12]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([C:31]5[CH:32]=[C:33]6[C:28]([CH:27]=[CH:26][NH:25]6)=[CH:29][CH:30]=5)=[CH:3][C:4]=4[F:24])[C:9](=[O:23])[NH:10][N:11]=3)[CH2:15]2)=[O:19])[CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27632051H-Indol-6-ylboronic acidHCID 67354682HCID 67354682, compound

Product 1

HCID 67375610HCID 67375610, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a microwave vial purged with nitrogen, a mixture of 4-(4-bromo-2-fluorophenyl)-5-{[1-(cyclopropylcarbonyl)-3-azetidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (64 mg, 0.162 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (15 mg, 0.018 mmol), and 1H-indol-6-ylboronic acid (30 mg, 0.186 mmol) in 1,4-dioxane (1.5 mL) and 2M aq potassium carbonate (0.5 mL, 1.000 mmol) were stirred at 100° C. in an oil bath for 16 h. The reaction was cooled to room temperature, diluted with ethyl acetate (10 mL), and then the layers were separated. The aqueous layer was neutralized using 1N aq HCl and then extracted with ethyl acetate (2×20 mL). The organic layers were combined, dried over MgSO4, and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-5% methanol/ethyl acetate) provided the title compound as an impure solid. Subsequent purification of this solid by reverse phase HPLC (10-70% acetonitrile/water+0.1% NH4OH) followed by dessication in a vacuum oven over the weekend provided the title compound as a white solid (16 mg, 23%). MS(ES)+ m/z 432.2 [M+H]+.

Workup

  1. customIn a microwave vial purged with nitrogen
  2. temperatureThe reaction was cooled to room temperature
  3. customthe layers were separated
  4. extractionextracted with ethyl acetate (2×20 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by silica gel chromatography (0-5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-9dbfba32c1b7402a8b6b95732a371321
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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