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

HRID 1498522Notes

Reaction equation

HRID 1498522 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]=[C:17]([CH3:23])[N:16]=4)[N:14]=[C:7]3[C:6]=2[CH:24]=1.[CH3:25][N:26](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N>[CH:20]([N:19]1[C:15]([C:13]2[N:14]=[C:7]3[C:6]4[CH:24]=[C:2]([C:25]#[N:26])[CH:3]=[CH:4][C:5]=4[O:11][CH2:10][CH2:9][N:8]3[CH:12]=2)=[N:16][C:17]([CH3:23])=[N:18]1)([CH3:22])[CH3:21]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 5820476010-bromo-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 582043712-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-10-carbonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A microwave vial was charged with a solution of 10-bromo-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (0.200 mg, 0.466 mmol) in 1.4 ml DMF. To this solution was added zinc cyanide (160 mg, 1.4 mmol). The reaction mixture was degassed by bubbling nitrogen through the stirred mixture via a syringe. After several minutes the syringe was removed and Bis(ditertbutyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (66 mg, 0.093 mmol) was added and the reaction vial was quickly sealed. The sealed vial was flash heated in a microwave at 150° C. for 30 minutes. The cooled reaction was diluted with EtOAc and the organic solution was washed with water ×1, saline ×1 and dried (Na2SO4) before concentration in vacuo. The crude residue was purified by preparative RP-HPLC to give 455. MS: (ESI+)=335.1

Workup

  1. customThe reaction mixture was degassed
  2. customby bubbling nitrogen through the stirred mixture via a syringe
  3. customAfter several minutes the syringe was removed
  4. customthe reaction vial was quickly sealed
  5. customThe cooled reaction
  6. washthe organic solution was washed with water ×1, saline ×1
  7. dry with materialdried (Na2SO4)
  8. concentrationbefore concentration in vacuo
  9. customThe crude residue was purified by preparative RP-HPLC

Sources & evidence

ORD record
ord-898fabcd55fd4980b6b5a5000d299986
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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