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]=1

Participants

Reactant 4

HCID 297Methane

HCID 887Methanol

HCID 14496Cyclobutanone

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

Product 1

HCID 717147229-Fluoro-10-((1-hydroxycyclobutyl)ethynyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

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).