Dimethylformamide → 10-Bromo-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 575017Notes

Reaction equation

HRID 575017 reaction equation
[Br:1][C:2]1[C:3]([F:17])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9](I)=[CH:10]3)[C:6]=2[CH:16]=1.C[Si](N[Si](C)(C)C)(C)C.C[N:28](C)[CH:29]=[O:30]>>[Br:1][C:2]1[C:3]([F:17])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:29]([NH2:28])=[O:30])=[CH:10]3)[C:6]=2[CH:16]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 13838HexamethyldisilazaneHCID 6831272510-Bromo-9-fluoro-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 8669305110-Bromo-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamideYield 30%

Conditions

Temperature
80 °C

Procedure

Into a 5000-mL pressure tank reactor (10 atm) purged and maintained with an inert atmosphere of nitrogen was placed 9-Bromo-8-fluoro-2-iodo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (204 g, 498.79 mmol, 1.00 equiv), HMDS (403.5 g, 2.50 mol, 5.00 equiv), Pd(PPh3)Cl2 (11 g, 25.02 mmol, 0.05 equiv), and N,N-dimethylformamide (3 L). To the above CO (10 atm) was introduced in. The resulting solution was stirred overnight at 80° C. and quenched by the addition of 5 L of water. The solids were collected by filtration. The crude product was re-crystallized from 800 mL of EA. The mixture was stirred at 50° C. for 3 h. The solids were collected by filtration, washed with 3×100 mL of EA and dried to afford 48.5 g (30%) of 9-Bromo-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a yellow solid. LC-MS: 326 [M+H]+; 1H-NMR (DMSO, 300 MHz, ppm): δ 8.75 (d, J=8.4 Hz, 1H), 7.79 (s, 1H), 7.61 (s, 1H), 7.16-7.11 (m, 2H), 4.49-4.50 (m, 4H).

Workup

  1. customInto a 5000-mL pressure tank reactor (10 atm) purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customquenched by the addition of 5 L of water
  4. filtrationThe solids were collected by filtration
  5. customThe crude product was re-crystallized from 800 mL of EA
  6. stirringThe mixture was stirred at 50° C. for 3 h
  7. filtrationThe solids were collected by filtration
  8. washwashed with 3×100 mL of EA
  9. customdried

Sources & evidence

ORD record
ord-127be2c116bc4701a89f56d22bc2f9fe
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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