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

HRID 1498246Notes

Reaction equation

HRID 1498246 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[CH:12]=[C:13](I)[N:14]=[C:7]3[C:6]=2[CH:16]=1.[CH:17]([N:20]1[CH:24]=[N:23][CH:22]=[N:21]1)([CH3:19])[CH3:18].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>CCOC(C)=O.[Cu]I.CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[CH:12]=[C:13]([C:24]4[N:20]([CH:17]([CH3:19])[CH3:18])[N:21]=[CH:22][N:23]=4)[N:14]=[C:7]3[C:6]=2[CH:16]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 127624431-(propan-2-yl)-1H-1,2,4-triazoleHCID 5820440710-Bromo-2-iodo-5,6-dihydrobenzo[F]imidazo[1,2-D][1,4]oxazepine

Product 1

HCID 5820501010-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 5.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To 10-bromo-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (1.5 g, 3.8 mmol), 1-isopropyl-1H-1,2,4-triazole (0.40 g, 3.0 mmol), CuI (1.8 g, 9.5 mmol), Pd(OAc)2 (0.071 g, 0.32 mmol), and cesium carbonate (2.6 g, 7.9 mmol) was added DMF (20 mL). The reaction mixture was allowed to stir and heat at 100° C. for 24 hours in a sealed vial. The reaction mixture was cooled to room temperature, diluted with EtOAc, and filtered through celite. The filtrate was concentrated under reduced pressure. To the crude residue was added EtOAc and the solid was collected by filtration. The filtrate was concentrated and the crude material was dissolved in DMF and purified by reverse phase HPLC to provide 187 (64 mg, 5%). 1H NMR (400 MHz, DMSO) δ 8.43 (dd, J=47.5, 31.0, 1H), 7.97 (s, 1H), 7.92 (s, 1H), 7.60-7.39 (m, 1H), 7.04 (d, J=8.7, 1H), 5.74 (dt, J=13.2, 6.6, 1H), 4.76-4.33 (m, 4H), 1.49 (d, J=6.6, 6H). MS(ESI(+)): m/z 374.0 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through celite
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. additionTo the crude residue was added EtOAc
  5. filtrationthe solid was collected by filtration
  6. concentrationThe filtrate was concentrated
  7. dissolutionthe crude material was dissolved in DMF
  8. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-1ec75df3ca2a4b828a779cb9ffd744c5
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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