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

HRID 909587Notes

Reaction equation

HRID 909587 reaction equation
[OH:1][C@H:2]([CH2:36][O:37][Si:38]([CH:45]([CH3:47])[CH3:46])([CH:42]([CH3:44])[CH3:43])[CH:39]([CH3:41])[CH3:40])[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][C@@H:2]([CH2:36][O:37][Si:38]([CH:45]([CH3:47])[CH3:46])([CH:39]([CH3:41])[CH3:40])[CH:42]([CH3:44])[CH3:43])[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:27])=[O:28])=[N:22][CH:21]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 66681179N-[(1R,2S)-2-Hydroxy-1-methyl-3-[(triisopropylsilyl)oxy]propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide

Product 1

HCID 666938995-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{5-[(4R,5R)-4-methyl-5-{[(triisopropylsilyl)oxy]methyl}-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-2-(methylsulfonyl)pyridineYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

N-[(1R,2S)-2-Hydroxy-1-methyl-3-[(triisopropylsilyl)oxy]propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide (1.69 g, 2.45 mmol) synthesized in Example (890 was dissolved in tetrahydrofuran (25 mL), and anhydrous methanesulfonic acid (0.88 g, 4.90 mmol) and triethylamine (1.37 mL, 9.80 mmol) were added, followed by stirring at 50° C. for 5 hours under nitrogen atmosphere. A saturated aqueous sodium hydrogencarbonate solution (40 mL) was added, and the solution was separated with ethyl acetate (60 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=10%-50%) to afford the desired compound (1.23 g, yield 75%) as a white solid.

Workup

  1. customthe solution was separated with ethyl acetate (60 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=10%-50%)

Sources & evidence

ORD record
ord-ce0f42bacadb417f808f9d9a0c20c9e0
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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