Methanesulfonic Acid → 5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{5-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-2-(methylsulfonyl)pyridine

HRID 1964632Notes

Reaction equation

HRID 1964632 reaction equation
[OH:1][CH2:2][C@H:3]([NH:5][C:6]([C:8]1[NH:9][C:10]([C:13]2[CH:18]=[C:17]([O:19][C:20]3[CH:21]=[N:22][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:24][CH:25]=3)[CH:16]=[C:15]([O:30][C@@H:31]([CH3:35])[CH2:32][O:33][CH3:34])[CH:14]=2)=[CH:11][CH:12]=1)=O)[CH3:4].CS(O)(=O)=O.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>O1CCCC1>[CH3:34][O:33][CH2:32][C@H:31]([CH3:35])[O:30][C:15]1[CH:16]=[C:17]([CH:18]=[C:13]([C:10]2[NH:9][C:8]([C:6]3[O:1][CH2:2][C@@H:3]([CH3:4])[N:5]=3)=[CH:12][CH:11]=2)[CH:14]=1)[O:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[N:22][CH:21]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 66682527N-[(1R)-2-Hydroxy-1-methylethyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide

Product 1

HCID 666814345-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{5-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-2-(methylsulfonyl)pyridineYield 85.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

N-[(1R)-2-Hydroxy-1-methylethyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide (1.94 g, 3.85 mmol) synthesized in Example (84a) was dissolved in tetrahydrofuran (35 mL), and anhydrous methanesulfonic acid (1.38 g, 7.70 mmol) and triethylamine (2.15 mL, 15.41 mmol) were added, followed by stirring at 50° C. for 1.5 hours under nitrogen atmosphere. A saturated aqueous sodium hydrogencarbonate solution (30 mL) was added, and the solution was separated with ethyl acetate (50 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: ethyl acetate/hexane=30%-75%) to afford the desired compound (1.59 g, yield 85%) as a white solid.

Workup

  1. customthe solution was separated with ethyl acetate (50 mL)
  2. washThe organic layer was washed with saturated brine
  3. dry with materialsubsequently dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=30%-75%)

Sources & evidence

ORD record
ord-eb83d1593e374d808783f0a05a526a30
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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