Potassium Carbonate → 3-[(8-Fluoro-2,3-dimethyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 548652Notes

Reaction equation

HRID 548652 reaction equation
C(=O)([O-])[O-].[K+].[K+].F[C:8]1[CH:20]=[CH:19][C:11]2[C:12](=[O:18])[N:13]([CH3:17])[CH2:14][CH2:15][O:16][C:10]=2[C:9]=1[F:21].[Si]([O:29][CH2:30][C@H:31]([CH3:49])[O:32][C:33]1[CH:34]=[C:35]([CH:45]=[C:46]([OH:48])[CH:47]=1)[C:36]([NH:38][C:39]1[CH:43]=[CH:42][N:41]([CH3:44])[N:40]=1)=[O:37])(C(C)(C)C)(C)C>CN1CCCC1=O>[F:21][C:9]1[C:10]2[O:16][CH:15]([CH3:14])[N:13]([CH3:17])[C:12](=[O:18])[C:11]=2[CH:19]=[CH:20][C:8]=1[O:48][C:46]1[CH:45]=[C:35]([CH:34]=[C:33]([O:32][C@@H:31]([CH3:49])[CH2:30][OH:29])[CH:47]=1)[C:36]([NH:38][C:39]1[CH:43]=[CH:42][N:41]([CH3:44])[N:40]=1)=[O:37]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 536296323-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamideHCID 57663183HCID 57663183, compound

Product 1

HCID 159491233-[(8-Fluoro-2,3-dimethyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 40.9%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

Potassium carbonate (152 mg, 1.1 mmol) was added to a solution of 8,9-difluoro-4-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-one (117 mg, 0.55 mmol) and 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (223 mg, 0.55 mmol) in 1-methyl-2-pyrrolidinone (10 mL) and the mixture heated at 140° C. for 3 days. The mixture was concentrated in vacuo and the residue suspended in ethyl acetate (20 mL). The suspension was filtered through Celite® and evaporated. The residue was purified by column chromatography (eluting with 0-20% methanol in DCM) to afford a colourless gum which solidified on evaporation from 30% methanol in DCM to afford the title compound as a colourless solid (109 mg, 33%).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. filtrationThe suspension was filtered through Celite®
  3. customevaporated
  4. customThe residue was purified by column chromatography (eluting with 0-20% methanol in DCM)
  5. customto afford a colourless gum which
  6. customsolidified on evaporation from 30% methanol in DCM

Sources & evidence

ORD record
ord-56baccb0d923450cbfe831fdd7501343
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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