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

HRID 575016Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:15](Cl)=[O:16])=[CH:10]3)[C:6]=2[CH:18]=1.[NH3:19]>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:15]([NH2:19])=[O:16])=[CH:10]3)[C:6]=2[CH:18]=1

Participants

Conditions

Temperature: 8 °C

Procedure

Into a 20 L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 9-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carbonyl chloride (460 g, 1.40 mol, 1.00 equiv) in tetrahydrofuran (4.5 L), followed by the addition ammonia (0° C.) (9 L) in one portion. The resulting solution was stirred at 0=8° C. for 5 h. The reaction progress was monitored by LCMS. The precipitates were collected by filtration, washed with 5×500 mL of water and 3×500 mL of EA, and dried in a vacuum oven to afford 300 g (69%) of 9-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as an off-white solid. LC-MS: 308 [M+H]+1H-NMR (300 MHz, DMSO, ppm): δ 4.48 (4H, s), 6.99-7.02 (1H, d), 7.16 (1H, s), 7.43-7.47 (1H, m), 7.59 (1H, s), 7.80 (1H, s), 8.62-8.63 (1H, d).

Workup

customInto a 20 L 4-necked round-bottom flask purged
temperaturemaintained with an inert atmosphere of nitrogen
filtrationThe precipitates were collected by filtration
washwashed with 5×500 mL of water and 3×500 mL of EA
customdried in a vacuum oven

Sources & evidence

ORD record: ord-e0904123659449e28d56242877cf15d1
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034866B2

Reaction notes

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