Ethyl Acetate → 3-[(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 548752Notes

Reaction equation

HRID 548752 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:37]=[CH:36][C:28]2[S:29](=[O:35])(=[O:34])[CH2:30][CH2:31][CH2:32][O:33][C:27]=2[CH:26]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C(#N)C.O>[O:35]=[S:29]1(=[O:34])[C:28]2[CH:36]=[CH:37][C:25]([O:1][C:2]3[CH:3]=[C:4]([CH:15]=[C:16]([O:18][C@@H:19]([CH3:23])[CH2:20][O:21][CH3:22])[CH:17]=3)[C:5]([NH:7][C:8]3[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=3)=[O:6])=[CH:26][C:27]=2[O:33][CH2:32][CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 576632198-fluoro-3,4-dihydro-2H-1,5-benzoxathiepine 5,5-dioxideHCID 59127168(S)-3-hydroxy-5-(1-methoxypropan-2-yloxy)-N-(5-methylpyrazin-2-yl)benzamide

Product 1

HCID 159499513-[(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)benzamideYield 34.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 3-hydroxy-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide (0.15 g, 0.47 mmol), 8-fluoro-3,4-dihydro-2H-1,5-benzoxathiepine 5,5-dioxide (103 mg, 0.47 mmol) and potassium carbonate (131 mg, 0.95 mmol) in acetonitrile (5 mL) was stirred in a microwave reactor at 160° C. for 5 hours. The mixture was reduced in vacuo and ethyl acetate (50 mL) and water (50 mL) were added. The aqueous layer was re-extracted into ethyl acetate (50 mL) and the combined organics washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and reduced in vacuo to give a golden oil. The oil was chromatographed on silica, eluting with 40-100% ethyl acetate in isohexane, to give the desired compound as a white foam (84 mg). 1H NMR δ (CDCl3): 1.34 (d, 3H), 2.39-2.47 (m, 2H), 2.56 (s, 3H), 3.34-3.37 (m, 2H), 3.41 (s, 3H), 3.49-3.61 (m, 2H), 4.24-4.27 (m, 2H), 4.58-4.65 (m, 1H), 6.76 (d, 1H), 6.85-6.88 (m, 2H), 7.16 (t, 1H), 7.35 (t, 1H), 7.94 (d, 1H), 8.14 (s, 1H), 8.30 (s, 1H), 9.53 (s, 1H); m/z 514 (M+H)+

Workup

  1. additionwere added
  2. extractionThe aqueous layer was re-extracted into ethyl acetate (50 mL)
  3. washthe combined organics washed with water (50 mL), brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customto give a golden oil
  7. customThe oil was chromatographed on silica
  8. washeluting with 40-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-fcc32e720a7d45c6854c2a7579ef6317
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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