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

HRID 575184Notes

Reaction equation

[Br:1][C:2]1[C:3]([F:17])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[CH:12]=[C:13](I)[N:14]=[C:7]3[C:6]=2[CH:16]=1.C[Si](N[Si](C)(C)C)(C)C.C[N:28](C)[CH:29]=[O:30]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:1][C:2]1[C:3]([F:17])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[CH:12]=[C:13]([C:29]([NH2:28])=[O:30])[N:14]=[C:7]3[C:6]=2[CH:16]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Similar to as described in Example 10, A suspension of 10-bromo-9-fluoro-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (16.0 g, 39.12 mmol, 1.00 equiv)(US2012/245144A1), HMDS (19.3 g, 119.88 mmol, 3.06 equiv) and Pd(dppf)Cl2 CH2Cl2 (1.6 g, 1.95 mmol, 0.05 equiv) in N,N-dimethylformamide (240 mL) was stirred for 2 h at 70° C. under a carbon monoxide atmosphere (1 atm). After cooling to room temperature the reaction was quenched by addition of methanol (5 mL), diluted by ethyl acetate (1 L), washed with water (200×4 mL) and brine (200 mL), dried over sodium sulfate, and concentrated under vacuum. The residue was further purified by FC(Silica and ethyl acetate/petroether 2:1) to give 7.0 g (55%) of the titled compound as a grey solid.

Workup

temperatureAfter cooling to room temperature the reaction
customwas quenched by addition of methanol (5 mL)
additiondiluted by ethyl acetate (1 L)
washwashed with water (200×4 mL) and brine (200 mL)
dry with materialdried over sodium sulfate
concentrationconcentrated under vacuum
customThe residue was further purified by FC(Silica and ethyl acetate/petroether 2:1)

Sources & evidence

ORD record: ord-2b646a4c911543769d8ce93216730eed
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034866B2

Reaction notes

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