Acetic Acid → HCID 66781514, compound

Participants

Reaction Steps

To a solution of 8-((trans)-3-fluoropiperidin-4-yloxy)-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinoline (Example 20; 185 mg, 0.42 mmol) in CH2Cl2 (5 mL) was added formaldehyde (316 μL, 37% in water, 4.2 mmol) followed by acetic acid (30 μL, 0.51 mmol) and sodium triacetoxyborohydride (270 mg, 1.27 mmol). The mixture was stirred vigorously at ambient temperature for 48 hours, then treated with 10% aq. K2CO3 (20 mL) and stirred for 10 minutes. The mixture was extracted with CH2Cl2, and the combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified via flash column chromatography using gradient elution (CH2Cl2 to 2% MeOH/CH2Cl2 to 5% MeOH/CH2Cl2) then dissolved in CHCl3 (5 mL) and treated with 4N HCl/dioxane (2 mL). After stirring for 20 minutes at ambient temperature the mixture was concentrated. The residue was triturated with ether, filtered and dried in vacuo to provide 136 mg (61%) of desired product as the di-HCl salt as a solid. MS APCI (+) m/z 451.2 (M+1) detected.

Provenance & Evidence