Trifluoroacetic acid → Methyl 6,6,6-trifluoro-N-({8-[(3-fluoropyridin-2-yl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridin-3-yl}carbonyl)-5-hydroxynorleucinate

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Reaction Steps

250 mg (0.71 mmol) of 8-[(3-fluoropyridin-2-yl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid hydrochloride from Example 121A, 299 mg (0.79 mmol) of HATU and 0.50 ml (2.85 mmol) of N,N-diisopropylethylamine were initially charged in 2.5 ml of DMF, and the mixture was stirred at RT for 20 min. 216 mg (0.86 mmol) of methyl 6,6,6-trifluoro-5-hydroxynorleucinate hydrochloride (stereoisomer mixture) were added, and the mixture was stirred at RT overnight. Water and TFA were added to the reaction solution and the product was purified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). The product fractions were concentrated, sodium bicarbonate solution was added to the residue and the mixture was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulphate, filtered off, concentrated and dried under high vacuum. This gave 265 mg (69% of theory) of the target compound.

Provenance & Evidence