2-Methyl-3-butyn-2-ol → (+/-)-3-((3,5-Difluorophenyl)(hydroxy)methyl)-9-fluoro-10-(3-hydroxy-3-methylbut-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 575384Notes

Reaction equation

HRID 575384 reaction equation
Br[C:2]1[C:3]([F:29])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12]([CH:18]([C:20]4[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=4)[OH:19])=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:28]=1.[CH3:30][C:31]([OH:35])([CH3:34])[C:32]#[CH:33]>>[F:27][C:22]1[CH:21]=[C:20]([CH:18]([OH:19])[C:12]2[N:8]3[CH2:9][CH2:10][O:11][C:5]4[CH:4]=[C:3]([F:29])[C:2]([C:33]#[C:32][C:31]([OH:35])([CH3:34])[CH3:30])=[CH:28][C:6]=4[C:7]3=[N:14][C:13]=2[C:15]([NH2:17])=[O:16])[CH:25]=[C:24]([F:26])[CH:23]=1

Participants

3

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 8669343110-Bromo-3-((3,5-difluorophenyl)(hydroxy)methyl)-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Product 1

HCID 86693432(+/-)-3-((3,5-Difluorophenyl)(hydroxy)methyl)-9-fluoro-10-(3-hydroxy-3-methylbut-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamideYield 45%

Procedure

3-((3,5-difluorophenyl)(hydroxy)methyl)-9-fluoro-10-(3-hydroxy-3-methylbut-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide was prepared similarly according to General Procedure G with slight modifications. 10-bromo-3-((3,5-difluorophenyl)(hydroxy)methyl)-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide was reacted with 3-methyl-1-butyne-3-ol to afford 25.7 mg of the titled compound (45% yield). M+1=472.1. 1H NMR (400 MHz, DMSO) δ 8.57 (d, J=8.4 Hz, 1H), 7.94 (br s, 1H), 7.47 (br s, 1H), 7.18-7.06 (m, 2H), 7.05-7.00 (m, 2H), 6.98 (d, J=10.6 Hz, 1H), 6.91-6.85 (m, 1H), 5.54 (s, 1H), 4.58-4.49 (m, 1H), 4.48-4.36 (m, 2H), 4.11-3.92 (m, 1H), 1.49 (s, 6H).

Workup

  1. custom3-((3,5-difluorophenyl)(hydroxy)methyl)-9-fluoro-10-(3-hydroxy-3-methylbut-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide was prepared similarly

Sources & evidence

ORD record
ord-b86d5505b8c240069e3a3ca1fa3e0da3
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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