Dimethylformamide → 10-(2-fluoropyridin-3-yl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1629235Notes

Reaction equation

HRID 1629235 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[CH:12]=[C:13]([C:15]4[N:19]([CH:20]([CH3:22])[CH3:21])[N:18]=[CH:17][N:16]=4)[N:14]=[C:7]3[C:6]=2[CH:23]=1.[F:24][C:25]1[C:30](B(O)O)=[CH:29][CH:28]=[CH:27][N:26]=1.C([O-])(=O)C.[K+].CN(C=O)C>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.O>[F:24][C:25]1[C:30]([C:2]2[CH:3]=[CH:4][C:5]3[O:11][CH2:10][CH2:9][N:8]4[CH:12]=[C:13]([C:15]5[N:19]([CH:20]([CH3:22])[CH3:21])[N:18]=[CH:17][N:16]=5)[N:14]=[C:7]4[C:6]=3[CH:23]=2)=[CH:29][CH:28]=[CH:27][N:26]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 517044Potassium AcetateHCID 27832702-Fluoropyridine-3-boronic acidHCID 5820501010-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 5820492510-(2-fluoropyridin-3-yl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 80.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
105 °C

Procedure

10-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 187 (0.057 g, 0.15 mmol), 2-fluoropyridin-3-ylboronic acid (0.026 g, 0.183 mmol), potassium acetate (0.059 g, 0.609 mmol), and tetrakis(triphenylphosphine)palladium(0) (8.8 mg, 0.007 mmol), DMF (6 mL) and water (0.6 mL) were mixed. Nitrogen was bubbled through the reaction mixture for 5 minutes. The reaction mixture was allowed to stir and heat at 105° C. for 24 hours before cooling, diluting with EtOAc, and filtering through a pad of celite. The filtrate was concentrated under reduced pressure and diluted with EtOAc. The solution was washed sequentially with water, and brine, before drying over MgSO4 and concentrating under reduced pressure. The crude material was dissolved in DMF and purified by reverse phase HPLC to provide 10-(2-fluoropyridin-3-yl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (47 mg, 80%). MS (ESI(+)): m/z 391.1 (M+H)

Workup

  1. customNitrogen was bubbled through the reaction mixture for 5 minutes
  2. temperaturebefore cooling
  3. additiondiluting with EtOAc
  4. filtrationfiltering through a pad of celite
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. additiondiluted with EtOAc
  7. washThe solution was washed sequentially with water, and brine
  8. dry with materialbefore drying over MgSO4
  9. concentrationconcentrating under reduced pressure
  10. dissolutionThe crude material was dissolved in DMF
  11. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-f6200f21942a430ca5093dfc879ad1cc
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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