Dimethylformamide → 9-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 1530420Notes

Reaction equation

HRID 1530420 reaction equation
[Br:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]3[N:7]([CH:11]=[C:12](I)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.C[Si](C)(C)N[Si](C)(C)C.C[N:27]([CH:29]=[O:30])C>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Br:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:29]([NH2:27])=[O:30])[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 13838HexamethyldisilazaneHCID 582048589-Bromo-2-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine

Product 1

HCID 582046299-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamideYield 62%

Reagents, catalysts & solvents 1

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
70 °C

Procedure

9-Bromo-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (1.5 g, 3.8 mmol) and bis(triphenylphosphine) palladium(II) chloride (142 mg, 0.202 mmol), DMF (45 mL) and hexamethyldisilazane (4.34 mL, 20.6 mmol) were mixed. The entire solution was purged with a CO balloon and sealed with the CO balloon attached. The reaction flask was heated at 70° C. for 2 h. LC/MS indicated clean conversion. Cooled to room temp and poured into 1 N HCl (30 mL). Stirred for 5 min and neutralized with sat. aq. NaHCO3 soln. Extracted three times with EtOAc, dried over MgSO4, filtered and concentrated in vacuo. Triturated with IPA and the solids were collected after filtration and EtOAc wash. This provided 734 mg (62% yield) of 9-bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide as a tan solid. LC/MS (ESI+): m/z 310 (M+H). 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J=8.5, 1H), 7.63 (s, 1H), 7.24 (dd, J=7.2, 4.2, 1H), 7.09-6.99 (m, 1H), 4.51-4.36 (m, 4H).

Workup

  1. customThe entire solution was purged with a CO balloon
  2. customsealed with the CO balloon
  3. temperatureCooled to room temp
  4. additionpoured into 1 N HCl (30 mL)
  5. extractionExtracted three times with EtOAc
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customTriturated with IPA
  10. customthe solids were collected
  11. filtrationafter filtration and EtOAc
  12. washwash

Sources & evidence

ORD record
ord-c4c68ccfd601466c91007cd1e05ba6f1
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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