Water → 3-[(9-Chloro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-5-[(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 548689Notes

Reaction equation

HRID 548689 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]([CH3:23])[C:12](=[O:22])[C:13]1[CH:18]=[CH:17][C:16](F)=[C:15]([Cl:20])[C:14]=1F)(C(C)(C)C)(C)C.[OH:24][C:25]1[CH:26]=[C:27]([CH:37]=[C:38]([O:40][CH:41]([CH3:43])[CH3:42])[CH:39]=1)[C:28]([NH:30][C:31]1[CH:35]=[CH:34][N:33]([CH3:36])[N:32]=1)=[O:29].C(=O)([O-])[O-].[K+].[K+].O>CC(N(C)C)=O>[Cl:20][C:15]1[C:14]2[O:8][CH2:9][CH2:10][N:11]([CH3:23])[C:12](=[O:22])[C:13]=2[CH:18]=[CH:17][C:16]=1[O:24][C:25]1[CH:26]=[C:27]([CH:37]=[C:38]([O:40][CH:41]([CH3:43])[CH3:42])[CH:39]=1)[C:28]([NH:30][C:31]1[CH:35]=[CH:34][N:33]([CH3:36])[N:32]=1)=[O:29]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 57663164N-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamideHCID 591271833-hydroxy-5-isopropoxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 159494943-[(9-Chloro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-5-[(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 33.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
135 °C

Procedure

N-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamide (705 mg, 1.94 mmol) was added to 3-hydroxy-5-[(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (512 mg, 1.86 mmol) and potassium carbonate (536 mg, 3.88 mmol) in DMA (25 mL) and the mixture was heated at 135° C. for 5 hours. Water (100 mL) was added and the reaction mixture extracted with ethyl acetate (3×30 mL). The combined organic phases were washed with water (2×30 mL), brine (2×30 mL), dried (MgSO4), filtered and evaporated. Purification by column chromatography on silica, eluting with 40-100% ethyl acetate in hexanes, afforded the desired compound as a pale yellow oil (300 mg). 1H NMR δ (CDCl3): 1.28 (d, 6H), 3.17 (s, 3H), 3.53 (t, 2H), 3.73 (s, 3H), 4.48 (t, 2H), 4.48-4.55 (m, 1H), 6.63 (t, 1H), 6.71 (d, 1H), 6.73 (d, 1H), 6.95 (t, 1H), 7.12 (t, 1H), 7.22 (d, 1H), 7.61 (d, 1H), 8.52 (s, 1H), m/z 485 (M+H)+ 483 (M−H)−

Workup

  1. extractionthe reaction mixture extracted with ethyl acetate (3×30 mL)
  2. washThe combined organic phases were washed with water (2×30 mL), brine (2×30 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customPurification by column chromatography on silica
  7. washeluting with 40-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-2d19852a16134954bbc418591739b06f
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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