2-Methyl-3-butyn-2-ol → (+/-)-3-((1,3-dimethyl-1H-pyrazol-4-yl) (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 575388Notes

Reaction equation

HRID 575388 reaction equation
Br[C:2]1[C:3]([F:28])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12]([CH:18]([C:20]4[C:21]([CH3:26])=[N:22][N:23]([CH3:25])[CH:24]=4)[OH:19])=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:27]=1.[CH3:29][C:30]([OH:34])([CH3:33])[C:31]#[CH:32]>>[CH3:25][N:23]1[CH:24]=[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:28])[C:2]([C:32]#[C:31][C:30]([OH:34])([CH3:33])[CH3:29])=[CH:27][C:6]=4[C:7]3=[N:14][C:13]=2[C:15]([NH2:17])=[O:16])[C:21]([CH3:26])=[N:22]1

Participants

3

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 8669343510-bromo-3-((1,3-dimethyl-1H-pyrazol-4-yl)(hydroxy)methyl)-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Product 1

HCID 86693436(+/-)-3-((1,3-dimethyl-1H-pyrazol-4-yl) (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 19%

Procedure

3-((1,3-dimethyl-1H-pyrazol-4-yl)(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-((1,3-dimethyl-1H-pyrazol-4-yl)(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 11.3 mg of the titled compound (19% yield). M+1=436.1. 1H NMR (400 MHz, DMSO) δ 8.58 (d, J=8.5 Hz, 1H), 7.87 (br s, 1H), 7.40 (br s, 1H), 7.25 (s, 1H), 6.99 (d, J=10.5 Hz, 1H), 6.72 (d, J=6.3 Hz, 1H), 6.52 (d, J=6.2 Hz, 1H), 5.54 (s, 1H), 4.58-4.25 (m, 4H), 3.65 (s, 3H), 2.06 (s, 3H), 1.49 (s, 6H).

Workup

  1. custom3-((1,3-dimethyl-1H-pyrazol-4-yl)(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-93482dc03a564f2fba34e185815eef81
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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