Trifluoroacetic acid → rac-8-[(3-fluoropyridin-2-yl)methoxy]-2,6-dimethyl-N-(3,3,3-trifluoro-2-hydroxypropyl)imidazo[1,2-a]pyridine-3-carboxamide

120 mg (0.34 mmol) of 8-[(3-fluoropyridin-2-yl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid hydrochloride from Example 121A, 169 mg (0.44 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (HATU) and 176 mg (1.37 mmol) of N,N-diisopropylethylamine were initially charged in 2.2 ml of DMF, the mixture was stirred for 50 min, 66 mg (0.51 mmol) of rac-3-amino-1,1,1-trifluoropropan-2-ol were then added and the mixture was stirred at RT for 1.5 h. A few drops of water and TFA were added to the reaction solution, and the product was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions were concentrated, and dichloromethane and saturated aqueous sodium bicarbonate solution were added to the residue. The aqueous phase was extracted three times with dichloromethane, the combined organic phases were dried over sodium sulphate and filtered and the filtrate was concentrated and lyophilized. This gave 49 mg (32% of theory) of the target compound.

1. stirringthe mixture was stirred at RT for 1.5 h
2. customthe product was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
3. concentrationThe product-containing fractions were concentrated
4. additiondichloromethane and saturated aqueous sodium bicarbonate solution were added to the residue
5. extractionThe aqueous phase was extracted three times with dichloromethane
6. dry with materialthe combined organic phases were dried over sodium sulphate
7. filtrationfiltered
8. concentrationthe filtrate was concentrated

ORD record

ord-633ae3f09c784e3c9351b7fa993f3b46

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946215B2