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Water → 3-[(7-Fluoro-5,5-dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide

HRID 548767
Notes
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Reaction equation

HRID 548767 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([O:18][C@@H:19]([CH3:23])[CH2:20][O:21][CH3:22])[CH:17]=1)[C:5]([NH:7][C:8]1[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=1)=[O:6].F[C:25]1[CH:30]=[C:29](F)[C:28]([F:32])=[CH:27][C:26]=1[S:33]([CH:36]1[CH2:40][CH2:39][O:38]C1=O)(=[O:35])=[O:34].C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[F:32][C:28]1[C:29]([O:1][C:2]2[CH:3]=[C:4]([CH:15]=[C:16]([O:18][C@@H:19]([CH3:23])[CH2:20][O:21][CH3:22])[CH:17]=2)[C:5]([NH:7][C:8]2[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=2)=[O:6])=[CH:30][C:25]2[O:38][CH2:39][CH2:40][CH2:36][S:33](=[O:35])(=[O:34])[C:26]=2[CH:27]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 576631723-[(2,4,5-trifluorophenyl)sulfonyl]dihydrofuran-2(3H)-oneHCID 59127168(S)-3-hydroxy-5-(1-methoxypropan-2-yloxy)-N-(5-methylpyrazin-2-yl)benzamide

Product 1

HCID 159500413-[(7-Fluoro-5,5-dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide
Yield 14.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-Hydroxy-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide (634 mg, 2 mmol), 3-[(2,4,5-trifluorophenyl)sulfonyl]dihydrofuran-2(3H)-one (560 mg, 2 mmol) and potassium carbonate (552 mg, 4 mmol) in acetonitrile (10 mL) were heated at 160° C. for 2 h and 170° C. for 30 minutes in a microwave reactor. Water was added to the reaction mixture and the phases separated. The aqueous phase was extracted with ethyl acetate (3×20 mL), and the combined organics washed with 1M hydrochloric acid, a saturated sodium bicarbonate solution, brine and dried (MgSO4) and evaporated. The residue was dissolved in methanol and heated to reflux on a steam bath. The residual solid was removed by hot filtration and the filtrate evaporated to a residue which was chromatographed on alumina, eluting with 10% methanol in DCM, to give the desired compound as a clear foam (152 mg). 1H NMR δ (CDCl3): 1.27 (d, 3H), 2.32-2.38 (m, 2H), 2.49 (s, 3H), 3.31 (t, 2H), 3.34 (s, 3H), 3.43-3.47 (m, 1H), 3.49-3.54 (m, 1H), 4.15 (t, 2H), 4.53-4.57 (m, 1H), 6.72 (d, 1H), 6.77 (t, 1H), 7.08 (t, 1H), 7.25 (t, 1H), 7.71-7.74 (m, 1H), 8.07 (d, 1H), 8.25 (s, 1H), 9.45 (d, 1H); m/z 532 (M+H)+, 530 (M−H)−

Workup

  1. customthe phases separated
  2. extractionThe aqueous phase was extracted with ethyl acetate (3×20 mL)
  3. washthe combined organics washed with 1M hydrochloric acid
  4. dry with materiala saturated sodium bicarbonate solution, brine and dried (MgSO4)
  5. customevaporated
  6. dissolutionThe residue was dissolved in methanol
  7. temperatureheated
  8. temperatureto reflux on a steam bath
  9. customThe residual solid was removed by hot filtration
  10. customthe filtrate evaporated to a residue which
  11. customwas chromatographed on alumina
  12. washeluting with 10% methanol in DCM

Sources & evidence

ORD record
ord-7a977c5d0fb842a69b7bb91b359e9f64
Source dataset
uspto-grants-2011_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07943607B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes