Methane → 9-Fluoro-10-((1-hydroxycyclobutyl)ethynyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide
Reaction equation
[C:1]1(=[O:5])[CH2:4][CH2:3][CH2:2]1.Br[C:7]1[C:8]([F:24])=[CH:9][C:10]2[O:16][CH2:15][CH2:14][N:13]3[CH:17]=[C:18]([C:20]([NH2:22])=[O:21])[N:19]=[C:12]3[C:11]=2[CH:23]=1.[CH4:25].[CH3:26]O>>[F:24][C:8]1[C:7]([C:25]#[C:26][C:1]2([OH:5])[CH2:4][CH2:3][CH2:2]2)=[CH:23][C:11]2[C:12]3[N:13]([CH:17]=[C:18]([C:20]([NH2:22])=[O:21])[N:19]=3)[CH2:14][CH2:15][O:16][C:10]=2[CH:9]=1Participants
Procedure
Cyclobutanone (0.2 g) was subjected to similar to as described in Procedure A to form crude 1-ethynylcyclobutanol which was reacted with 10-bromo-9-fluoro-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide (0.1 g) via similar to as described in Procedure E to afford 33.8 mg of 9-fluoro-10-((1-hydroxycyclobutyl)ethynyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide after triteration from methanol and activated charcoal treatment. The mother liquor was concentrated and purified by reverse phase hplc to afford and additional 8.9 mg of product. MS (Q1) 342 (M)+. 1H NMR (400 MHz, DMSO) δ 8.59 (d, J=8.5 Hz, 1H), 7.78 (s, 1H), 7.57 (s, 1H), 7.12 (s, 1H), 7.01 (d, J=10.6 Hz, 1H), 5.94 (s, 1H), 4.50 (dd, J=14.9, 5.3 Hz, 4H), 2.44-2.36 (m, 2H), 2.23 (m, 3H), 1.89-1.70 (m, 2H).
Workup
- customto form crude 1-ethynylcyclobutanol which
Sources & evidence
- ORD record
- ord-5d97a7bbf9e94e6686edb4f3207c0f6d
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09034866B2
Reaction notes
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