Water → 5-(3-{5-[(5R)-5-(Hydroxymethyl)-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-[(1S)-2-methoxy-1-methylethoxy]phenoxy)-N-methylpyridine-2-carboxamide

HRID 1964728Notes

Reaction equation

HRID 1964728 reaction equation
F[C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][CH3:11])=[O:9])=[N:6][CH:7]=1.[OH:12][CH2:13][C@@H:14]1[O:18][C:17]([C:19]2[NH:23][C:22]([C:24]3[CH:25]=[C:26]([OH:36])[CH:27]=[C:28]([O:30][C@@H:31]([CH3:35])[CH2:32][O:33][CH3:34])[CH:29]=3)=[CH:21][CH:20]=2)=[N:16][CH2:15]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[OH:12][CH2:13][C@@H:14]1[O:18][C:17]([C:19]2[NH:23][C:22]([C:24]3[CH:25]=[C:26]([CH:27]=[C:28]([O:30][C@@H:31]([CH3:35])[CH2:32][O:33][CH3:34])[CH:29]=3)[O:36][C:2]3[CH:3]=[CH:4][C:5]([C:8]([NH:10][CH3:11])=[O:9])=[N:6][CH:7]=3)=[CH:21][CH:20]=2)=[N:16][CH2:15]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 666814253-{5-[(5R)-5-(Hydroxylmethyl)-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-[(1S)-2-methoxy-1-methylethoxy]phenolHCID 666833945-fluoro-N-methylpyridine-2-carboxamide

Product 1

HCID 666817705-(3-{5-[(5R)-5-(Hydroxymethyl)-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-[(1S)-2-methoxy-1-methylethoxy]phenoxy)-N-methylpyridine-2-carboxamideYield 60.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

5-Fluoro-N-methylpyridine-2-carboxamide (150 mg, 0.97 mmol) synthesized in Example (123a) and 3-{5-[(5R)-5-(hydroxylmethyl)-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-[(1S)-2-methoxy-1-methylethoxy]phenol (438 mg, 1.27 mmol) synthesized in Example (125g) were dissolved in N,N-dimethylformamide (3 mL), and potassium carbonate (269 mg, 1.95 mmol) was added, followed by stirring at 100° C. for 3 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (30 mL) was added, and extraction was carried out twice with ethyl acetate (30 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: methanol/methylene chloride=0%-5%) to afford the desired compound (281 mg, yield 60%) as a white solid.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextraction
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: methanol/methylene chloride=0%-5%)

Sources & evidence

ORD record
ord-89a35c8189044f7caabc6c4ef84b2245
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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