Potassium Carbonate → 3-{[4-(Azetidin-1-ylcarbonyl)-2-fluorophenyl]oxy}-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide

HRID 20515Notes

Reaction equation

HRID 20515 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:9]=[C:10]([CH:21]=[C:22]([O:24][C@@H:25]([CH3:28])[CH2:26][OH:27])[CH:23]=1)[C:11]([NH:13][C:14]1[CH:19]=[N:18][C:17]([CH3:20])=[CH:16][N:15]=1)=[O:12].[F:29][C:30]1[CH:31]=[C:32]([CH:39]=[CH:40][C:41]=1F)[C:33]([N:35]1[CH2:38][CH2:37][CH2:36]1)=[O:34]>C(#N)C>[N:35]1([C:33]([C:32]2[CH:39]=[CH:40][C:41]([O:7][C:8]3[CH:9]=[C:10]([CH:21]=[C:22]([O:24][C@@H:25]([CH3:28])[CH2:26][OH:27])[CH:23]=3)[C:11]([NH:13][C:14]3[CH:19]=[N:18][C:17]([CH3:20])=[CH:16][N:15]=3)=[O:12])=[C:30]([F:29])[CH:31]=2)=[O:34])[CH2:38][CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 591271143-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamideHCID 593468591-(3,4-Difluorobenzoyl)azetidine

Product 1

HCID 115331033-{[4-(Azetidin-1-ylcarbonyl)-2-fluorophenyl]oxy}-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamideYield 10.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

Potassium carbonate (182 mg, 1.32 mmol) was added to a mixture of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide (200 mg, 0.66 mmol) and 1-(3,4-difluorobenzoyl)azetidine (137 mg, 0.69 mmol) in acetonitrile (5.0 mL) and the stirred mixture heated at 160° C. in a ‘Smith Creator Microwave’ for 4 hours. The mixture was allowed to reach ambient temperature and pressure and reduced in vacuo. The residual oil was partitioned between ethyl acetate (50 mL) and water (50 mL). The ethyl acetate layer was separated, washed with brine, dried (MgSO4), and evaporated to a residue which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (34 mg).

Workup

  1. customto reach ambient temperature
  2. customThe residual oil was partitioned between ethyl acetate (50 mL) and water (50 mL)
  3. customThe ethyl acetate layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated to a residue which
  7. customwas chromatographed on silica
  8. washeluting with a gradient of 50-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-e33a1f5566ad4ef48f0ee291c5a41c68
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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