Potassium Carbonate → 3-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(5-methyl-1,3-thiazol-2-yl)benzamide

HRID 20563Notes

Reaction equation

HRID 20563 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[S:15][C:16]([CH3:19])=[CH:17][N:18]=1)=[O:12].[F:28][C:29]1[CH:30]=[C:31]([CH:38]=[CH:39][C:40]=1F)[C:32]([N:34]1[CH2:37][CH2:36][CH2:35]1)=[O:33]>C(#N)C>[N:34]1([C:32]([C:31]2[CH:38]=[CH:39][C:40]([O:7][C:8]3[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=3)[C:11]([NH:13][C:14]3[S:15][C:16]([CH3:19])=[CH:17][N:18]=3)=[O:12])=[C:29]([F:28])[CH:30]=2)=[O:33])[CH2:37][CH2:36][CH2:35]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 593468591-(3,4-Difluorobenzoyl)azetidineHCID 593469303-hydroxy-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(5-methyl-1,3-thiazol-2-yl)benzamide

Product 1

HCID 115911873-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(5-methyl-1,3-thiazol-2-yl)benzamideYield 11.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

Potassium carbonate (143 mg, 1.04 mmol) was added to a mixture of 3-hydroxy-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(5-methyl-1,3-thiazol-2-yl)benzamide (160 mg, 0.52 mmol) and 1-(3,4-difluorobenzoyl)azetidine (102 mg, 0.52 mmol) in acetonitrile (5.0 mL), and the stirred mixture heated at 160° C. in a ‘Smith Creator Microwave’ for 15 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 0-10% methanol in ethyl acetate, to give the desired compound (30 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 0-10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-308b3bcc3e194fc995cb9ff11d2ac7bb
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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