4-Methylmorpholine → N-[(1R)-1-(Hydroxymethyl)propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide

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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), (R)-(−)-2-amino-1-butanol (0.38 mL, 4.03 mmol), HOBT•H2O (0.44 g, 3.23 mmol) and N-methylmorpholine (0.59 mL, 5.38 mmol) were dissolved in methylene chloride (30 mL), and WSCI•HCl (0.62 g, 3.23 mmol) was added at room temperature, followed by stirring for 6 hours under nitrogen atmosphere. The reaction solution was diluted with methylene chloride (50 mL), washed with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and 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=50%-90%) to afford the desired compound (1.18 g, 85%) as a white solid.

Provenance & Evidence