Potassium Carbonate → N-(1-methyl-1H-pyrazol-3-yl)-3-[(phenylmethyl)oxy]-5-[(3R)-tetrahydrofuran-3-yloxy]benzamide

HRID 1011801Notes

Reaction equation

HRID 1011801 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].CC1C=CC(S(O[C@H:36]2[CH2:40][CH2:39][O:38][CH2:37]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH3:13][N:10]1[CH:11]=[CH:12][C:8]([NH:7][C:5](=[O:6])[C:4]2[CH:3]=[C:2]([O:1][C@@H:36]3[CH2:40][CH2:39][O:38][CH2:37]3)[CH:16]=[C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:14]=2)=[N:9]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 13837326(S)-tetrahydrofuran-3-yl 4-methylbenzenesulfonateHCID 591271193-(Benzyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 53629682N-(1-methyl-1H-pyrazol-3-yl)-3-[(phenylmethyl)oxy]-5-[(3R)-tetrahydrofuran-3-yloxy]benzamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

A suspension of 3-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)-5-[(phenylmethyl)oxy]benzamide (450 mg, 1.39 mmol), (3S)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (507 mg, 2.09 mmol) and potassium carbonate (481 mg, 3.48 mmol) in acetonitrile (5 mL) was stirred in a microwave reactor at 160° C. for 3 hours. The solvent was removed in vacuo and ethyl acetate added. The organics were washed with water (40 mL), brine (40 mL), dried (MgSO4), filtered and the solvent removed in vacuo. The residue was chromatographed on silica, eluting with a gradient of 0-100% ethyl acetate in isohexane, to give N-(1-methyl-1H-pyrazol-3-yl)-3-[(phenylmethyl)oxy]-5-[(3R)-tetrahydrofuran-3-yloxy]benzamide as a white foam. This was dissolved in ethanol (5 mL) and ammonium formate (182 mg, 2.88 mmol) added in one portion. The reaction was blanketed with argon and 10% palladium on activated carbon (30 mg) was added. This mixture was heated in a microwave reactor at 140° C. for 10 minutes, the catalyst filtered off and the volatiles removed in vacuo to give the title product as a white solid (305 mg).

Workup

  1. customThe solvent was removed in vacuo and ethyl acetate
  2. additionadded
  3. washThe organics were washed with water (40 mL), brine (40 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customThe residue was chromatographed on silica
  8. washeluting with a gradient of 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-03c204a963444ebc8914e8a10ee89d65
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

Loading…