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-(4-methoxybenzyl)-N-methylpyridine-2-sulfonamide

HRID 1964729Notes

Reaction equation

HRID 1964729 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH3:12])(=[O:10])=[O:9])=[N:6][CH:7]=1.[OH:22][CH2:23][C@@H:24]1[O:28][C:27]([C:29]2[NH:33][C:32]([C:34]3[CH:35]=[C:36]([OH:46])[CH:37]=[C:38]([O:40][C@@H:41]([CH3:45])[CH2:42][O:43][CH3:44])[CH:39]=3)=[CH:31][CH:30]=2)=[N:26][CH2:25]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[OH:22][CH2:23][C@@H:24]1[O:28][C:27]([C:29]2[NH:33][C:32]([C:34]3[CH:35]=[C:36]([CH:37]=[C:38]([O:40][C@@H:41]([CH3:45])[CH2:42][O:43][CH3:44])[CH:39]=3)[O:46][C:2]3[CH:3]=[CH:4][C:5]([S:8]([N:11]([CH2:13][C:14]4[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=4)[CH3:12])(=[O:10])=[O:9])=[N:6][CH:7]=3)=[CH:31][CH:30]=2)=[N:26][CH2:25]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 666813895-Chloro-N-(4-methoxybenzyl)-N-methylpyridine-2-sulfonamideHCID 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 666833095-(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-(4-methoxybenzyl)-N-methylpyridine-2-sulfonamideYield 27.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

5-Chloro-N-(4-methoxybenzyl)-N-methylpyridine-2-sulfonamide (427 mg, 1.31 mmol) synthesized in Example (121b) 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 (568 mg, 1.64 mmol) synthesized in Example (125g) were dissolved in N,N-dimethylformamide (5 mL), and potassium carbonate (361 mg, 2.61 mmol) was added, followed by stirring at 100° C. for 2 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (40 mL) was added, and extraction was carried out twice with ethyl acetate (40 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%-3.5%) to afford the desired compound (228 mg, yield 27%) 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%-3.5%)

Sources & evidence

ORD record
ord-74becd6ee66a41939eca2637a6c22286
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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