Potassium Carbonate → 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 1989919Notes

Reaction equation

HRID 1989919 reaction equation
[F:1][CH2:2][CH:3]([O:6][C:7]1[CH:8]=[C:9]([CH:19]=[C:20]([OH:22])[CH:21]=1)[C:10]([NH:12][C:13]1[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=1)=[O:11])[CH2:4][F:5].[N:23]1([C:27]([C:29]2[CH:30]=[C:31]([Cl:36])[C:32](Cl)=[N:33][CH:34]=2)=[O:28])[CH2:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[N:23]1([C:27]([C:29]2[CH:30]=[C:31]([Cl:36])[C:32]([O:22][C:20]3[CH:19]=[C:9]([CH:8]=[C:7]([O:6][CH:3]([CH2:2][F:1])[CH2:4][F:5])[CH:21]=3)[C:10]([NH:12][C:13]3[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=3)=[O:11])=[N:33][CH:34]=2)=[O:28])[CH2:26][CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 536296165-(Azetidin-1-ylcarbonyl)-2,3-dichloropyridineHCID 591271643-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 160401483-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 73.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (200 mg, 0.64 mmol), 5-(azetidin-1-ylcarbonyl)-2,3-dichloropyridine (164 mg, 0.71 mmol) and potassium carbonate (178 mg, 1.28 mmol) in acetonitrile (5 mL) was stirred in a ‘Biotage initiator Microwave’ at 120° C. for 4 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acetate and water (100 mL), the organic layer washed with brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a brown oil which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (237 mg).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between ethyl acetate and water (100 mL)
  3. washthe organic layer washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customto give a brown oil which
  8. customwas chromatographed on silica
  9. washeluting with a gradient of 50-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-1454cd8545fa4021ac77d9bd761ba84d
Source dataset
uspto-grants-2010_01
Patent number
US07642263B2

Reaction notes

Loading…