Water → 3-[(9-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 548705Notes

Reaction equation

HRID 548705 reaction equation
CC([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]([CH3:21])[C:10](=[O:20])[C:11]1[CH:16]=[CH:15][C:14](F)=[C:13]([F:18])[C:12]=1F)(C)C.[OH:24][C:25]1[CH:26]=[C:27]([CH:37]=[C:38]([O:40][C@@H:41]([CH3:45])[CH2:42][O:43][CH3:44])[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>[F:18][C:13]1[C:12]2[O:6][CH2:7][CH2:8][N:9]([CH3:21])[C:10](=[O:20])[C:11]=2[CH:16]=[CH:15][C:14]=1[O:24][C:25]1[CH:26]=[C:27]([CH:37]=[C:38]([O:40][C@@H:41]([CH3:45])[CH2:42][O:43][CH3:44])[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 57663171N-(2-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}ethyl)-2,3,4-trifluoro-N-methylbenzamideHCID 591271783-hydroxy-5-{[(2S)-1-methoxypropan-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 159495893-[(9-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 75.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

A suspension of N-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-2,3,4-trifluoro-N-methylbenzamide (300 mg, 0.86 mmol), 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (278 mg, 0.91 mmol) and potassium carbonate (237 mg, 1.73 mmol) in DMA (20 mL) was heated to 140° C. for 1 hour. The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with brine (50 mL) and dried (MgSO4), filtered and evaporated to give an orange oil. This was purified via column chromatography on silica, eluting with 50-100% ethyl acetate in isohexane, to give the desired product as a colourless oil (322 mg). 1H NMR δ (CDCl3): 1.25 (d, 3H), 2.77 (s, 3H), 3.33 (s, 3H), 3.44 (dd, 1H), 3.50 (dd, 1H), 3.71 (s, 3H), 3.74 (t, 2H), 4.25 (t, 2H), 4.49-4.56 (m, 1H), 6.71 (d, 1H), 6.73 (t, 1H), 6.75 (dd, 1H), 7.04 (t, 1H), 7.20-7.20 (m, 1H), 7.22 (d, 1H), 7.47 (dd, 1H), 8.68 (s, 1H); m/z 499 (M+H)+

Workup

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. washThe combined organic phases were washed with brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give an orange oil
  7. customThis was purified via column chromatography on silica
  8. washeluting with 50-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-a2e28474dd8245f08b91bd557c433a84
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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