Triethylamine → N-[(1R,2R)-2-Hydroxy-1-{[(triisopropylsilyl)oxy]methyl}propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide

HRID 1964650Notes

Reaction equation

HRID 1964650 reaction equation
[OH:1][C@H:2]([CH3:37])[C@H:3]([NH:6][C:7]([C:9]1[NH:10][C:11]([C:14]2[CH:19]=[C:18]([O:20][C:21]3[CH:22]=[N:23][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][CH:26]=3)[CH:17]=[C:16]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][CH3:35])[CH:15]=2)=[CH:12][CH:13]=1)=[O:8])[CH2:4][OH:5].C(N(CC)CC)C.[CH:45]([Si:48](Cl)([CH:52]([CH3:54])[CH3:53])[CH:49]([CH3:51])[CH3:50])([CH3:47])[CH3:46]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[OH:1][C@H:2]([CH3:37])[C@H:3]([NH:6][C:7]([C:9]1[NH:10][C:11]([C:14]2[CH:19]=[C:18]([O:20][C:21]3[CH:22]=[N:23][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:25][CH:26]=3)[CH:17]=[C:16]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][CH3:35])[CH:15]=2)=[CH:12][CH:13]=1)=[O:8])[CH2:4][O:5][Si:48]([CH:52]([CH3:54])[CH3:53])([CH:49]([CH3:51])[CH3:50])[CH:45]([CH3:47])[CH3:46]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 139400Triisopropylsilyl chlorideHCID 66681438N-[(1R,2R)-2-Hydroxy-1-(hydroxymethyl)propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide

Product 1

HCID 66683586N-[(1R,2R)-2-Hydroxy-1-{[(triisopropylsilyl)oxy]methyl}propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamideYield 90.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

N-[(1R,2R)-2-Hydroxy-1-(hydroxymethyl)propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide (883 mg, 1.65 mmol) synthesized in Example (91a), triethylamine (1.15 mL, 8.27 mmol) and 4-dimethylaminopyridine (404 mg, 3.31 mmol) were dissolved in methylene chloride (20 mL), and triisopropylsilyl chloride (0.60 mL, 2.81 mmol) was added at room temperature, followed by stirring for 20 hours under nitrogen atmosphere. 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%-60%) to afford the desired compound (1.03 g, 90%) as a white solid.

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. customthe resulting residue was purified
  3. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=30%-60%)

Sources & evidence

ORD record
ord-902097e54076488ea927b058d41709ab
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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