4-Methylmorpholine → 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

Participants

Reaction Steps

5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid (1.20 g, 2.69 mmol) synthesized in Example (78k), (2S,3R)-3-amino-1-[(tripropan-2-ylsilyl)oxy]butan-2-ol (1.08 g, 4.11 mmol) synthesized in Example (89e), HOBT•H2O (0.44 g, 3.23 mmol) and N-methylmorpholine (0.59 mL, 5.38 mmol) were dissolved in N,N-dimethylformamide (20 mL), and WSCI•HCl (0.62 g, 3.23 mmol) was added at room temperature, followed by stirring for 18 hours under nitrogen atmosphere. To the reaction solution, saturated brine (30 mL) was added, and extraction was carried out with ethyl acetate (60 mL). After washing with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, drying was carried out 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=20%-50%) to afford the desired compound (1.69 g, 91%) as a white powder.

Provenance & Evidence