Water → {(5R)-2-[5-(3-{[6-(Cyclopropylsulfonyl)pyridin-3-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-5-yl}methanol

HRID 909672Notes

Reaction equation

HRID 909672 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH:11]2[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[N:6][CH:7]=1.[OH:14][CH2:15][C@@H:16]1[O:20][C:19]([C:21]2[NH:25][C:24]([C:26]3[CH:27]=[C:28]([OH:38])[CH:29]=[C:30]([O:32][C@@H:33]([CH3:37])[CH2:34][O:35][CH3:36])[CH:31]=3)=[CH:23][CH:22]=2)=[N:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH:11]1([S:8]([C:5]2[N:6]=[CH:7][C:2]([O:38][C:28]3[CH:27]=[C:26]([C:24]4[NH:25][C:21]([C:19]5[O:20][C@@H:16]([CH2:15][OH:14])[CH2:17][N:18]=5)=[CH:22][CH:23]=4)[CH:31]=[C:30]([O:32][C@@H:33]([CH3:37])[CH2:34][O:35][CH3:36])[CH:29]=3)=[CH:3][CH:4]=2)(=[O:10])=[O:9])[CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 666814225-Chloro-2-(cyclopropylsulfonyl)pyridineHCID 666814253-{5-[(5R)-5-(Hydroxylmethyl)-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-[(1S)-2-methoxy-1-methylethoxy]phenol

Product 1

HCID 58065511{(5R)-2-[5-(3-{[6-(Cyclopropylsulfonyl)pyridin-3-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-5-yl}methanolYield 34.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

5-Chloro-2-(cyclopropylsulfonyl)pyridine (168 mg, 0.77 mmol) synthesized in Example (125c) 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 (401 mg, 1.16 mmol) synthesized in Example (125g) were dissolved in N,N-dimethylformamide (2 mL), and potassium carbonate (213 mg, 154 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%-5%) to afford the desired compound (139 mg, yield 34%) 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%-5%)

Sources & evidence

ORD record
ord-d7411f4ae33c4cc996023a7ca02e779e
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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