N-Iodosuccinimide → 10-Bromo-9-fluoro-3-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 575018Notes

Reaction equation

HRID 575018 reaction equation
[Br:1][C:2]1[C:3]([F:19])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:15]([NH2:17])=[O:16])=[CH:10]3)[C:6]=2[CH:18]=1.C1C(=O)N([I:27])C(=O)C1>CS(C)=O>[Br:1][C:2]1[C:3]([F:19])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:15]([NH2:17])=[O:16])=[C:10]3[I:27])[C:6]=2[CH:18]=1

Participants

4

Reactant 2

HCID 120273N-IodosuccinimideHCID 8669305110-Bromo-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Product 1

HCID 8669305210-Bromo-9-fluoro-3-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamideYield 47.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

Into a 3000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 9-Bromo-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide (150 g, 459.95 mmol, 1.00 equiv) in DMSO (1500 mL), and NIS (206.1 g, 916.08 mmol, 2.00 equiv). The resulting solution was stirred overnight at 80° C., cooled to room temperature, quenched by the addition of 6 L of water, and diluted with 600 mL of saturated aqueous Na2SO3 and 600 mL saturated aqueous Na2CO3. The solids were collected by filtration and washed with 5×300 mL of water. The crude product was purified by Flash-Prep-HPLC to afford 98 g (47%) of 9-Bromo-8-fluoro-3-iodo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a light brown solid. LC-MS: 452 [M+H]+: 1H-NMR (DMSO, 300 MHz, ppm): δ 8.80 (d, J=8.1 Hz, 1H), 7.76 (s, 1H), 7.20 (s, 1H), 7.14 (d, J=9.6 Hz, 1H), 4.57-4.54 (m, 2H), 4.39-4.36 (m, 2H).

Workup

  1. customInto a 3000-mL 4-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperaturecooled to room temperature
  4. customquenched by the addition of 6 L of water
  5. additiondiluted with 600 mL of saturated aqueous Na2SO3 and 600 mL saturated aqueous Na2CO3
  6. filtrationThe solids were collected by filtration
  7. washwashed with 5×300 mL of water
  8. customThe crude product was purified by Flash-Prep-HPLC

Sources & evidence

ORD record
ord-66c10bf50df34ceea07b94170cd9d7b7
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

Loading…