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-methylpyrazine-2-sulfonamide

HRID 1964730Notes

Reaction equation

HRID 1964730 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([S:8]([NH:11][CH3:12])(=[O:10])=[O:9])=[N:6][CH:7]=1.[OH:13][CH2:14][C@@H:15]1[O:19][C:18]([C:20]2[NH:24][C:23]([C:25]3[CH:26]=[C:27]([OH:37])[CH:28]=[C:29]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][CH3:35])[CH:30]=3)=[CH:22][CH:21]=2)=[N:17][CH2:16]1.C(=O)([O-])[O-].[K+].[K+].O>C(#N)C.C(OCC)(=O)C>[OH:13][CH2:14][C@@H:15]1[O:19][C:18]([C:20]2[NH:24][C:23]([C:25]3[CH:26]=[C:27]([CH:28]=[C:29]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][CH3:35])[CH:30]=3)[O:37][C:2]3[N:3]=[CH:4][C:5]([S:8]([NH:11][CH3:12])(=[O:10])=[O:9])=[N:6][CH:7]=3)=[CH:22][CH:21]=2)=[N:17][CH2:16]1

Participants

7

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 866495755-Bromo-N-methylpyrazine-2-sulfonamide

Product 1

HCID 666813115-(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-methylpyrazine-2-sulfonamideYield 54%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Bromo-N-methylpyrazine-2-sulfonamide (147 mg, 0.58 mmol) synthesized in Example (128b) 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 (262 mg, 0.76 mmol) synthesized in Example (125g) were dissolved in acetonitrile (6 mL), and potassium carbonate (161 mg, 1.17 mmol) was added, followed by stirring for 4 hours under nitrogen atmosphere. Water (20 mL) was added to the reaction solution, and extraction was carried out twice with ethyl acetate (20 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 (161 mg, yield 54%) as a white solid.

Workup

  1. washThe organic layer was washed with saturated brine
  2. dry with materialsubsequently dried over anhydrous magnesium sulfate
  3. distillationThe solvent was distilled off under reduced pressure
  4. customthe resulting residue was purified
  5. washsilica gel column chromatography (elution solvent: methanol/methylene chloride=0%-3.5%)

Sources & evidence

ORD record
ord-111d11a52e3a471a965ab228c2570d9f
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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