Water → 3-[(7-Fluoro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 548706Notes

Reaction equation

HRID 548706 reaction equation
[F:1][C:2]1[C:3](F)=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]([CH3:12])[C:7](=[O:13])[C:6]=2[CH:14]=1.[OH:16][C:17]1[CH:18]=[C:19]([CH:29]=[C:30]([O:32][C@@H:33]([CH3:37])[CH2:34][O:35][CH3:36])[CH:31]=1)[C:20]([NH:22][C:23]1[CH:27]=[CH:26][N:25]([CH3:28])[N:24]=1)=[O:21].C(=O)([O-])[O-].[K+].[K+].O>CC(N(C)C)=O>[F:1][C:2]1[C:3]([O:16][C:17]2[CH:18]=[C:19]([CH:29]=[C:30]([O:32][C@@H:33]([CH3:37])[CH2:34][O:35][CH3:36])[CH:31]=2)[C:20]([NH:22][C:23]2[CH:27]=[CH:26][N:25]([CH3:28])[N:24]=2)=[O:21])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]([CH3:12])[C:7](=[O:13])[C:6]=2[CH:14]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 576632107,8-difluoro-4-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-oneHCID 591271783-hydroxy-5-{[(2S)-1-methoxypropan-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 159495903-[(7-Fluoro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 6.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 7,8-difluoro-4-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-one (725 mg, 2.0 mmol), 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (600 mg, 1.97 mmol) and potassium carbonate (550 mg, 3.88 mmol) in DMA (10 mL) was heated to 160° C. for 5 hours. Water (20 mL) was added to the reaction and extracted with ethyl acetate (3×30 mL). The combined organic phases were washed with water (2×30 mL) and brine (2×30 mL), dried (MgSO4), filtered and evaporated to give a yellow oil. This was purified by column chromatography on silica, eluting with 20-100% ethyl acetate in isohexane, to give the desired compound as a foam (65 mg).

Workup

  1. extractionextracted with ethyl acetate (3×30 mL)
  2. washThe combined organic phases were washed with water (2×30 mL) and brine (2×30 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give a yellow oil
  7. customThis was purified by column chromatography on silica
  8. washeluting with 20-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-ac7b4d1ea0e3455bbbbfa3052160a471
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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