To a 100 mL round-bottomed flask was added (1S)-1-(hydroxymethyl)-1,2,5,6-tetrahydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione HCl (for a preparation see Example 47(c)) (350 mg, 1.589 mmol), triethylamine (0.266 ml, 1.907 mmol) in DCM (20 ml) 0° C. to give a orange solution. Methane sulfonylchloride (0.135 ml, 1.748 mmol) was added and the reaction was allowed to warm to rt and stir for 1 h. LCMS indicated that the methanesulfonate had formed. The reaction was diluted with DCM (100 mL) and washed with 2×25 mL of a saturated aqueous NaHCO3 solution. The organic phase was separated and dried over Na2SO4. The solution was concentrated under vacuum, diluted with acetonitrile (20.00 ml) and pyridine (0.500 ml) was added. 2,2,2-trifluoro-N-[(3R)-3-pyrrolidinylmethyl]acetamide (550 mg, 2.364 mmol) was added and the reaction was heated to 80° C. and stirred for 25 h. LCMS indicated a complete reaction. The reaction was cooled to rt and concentrated under vacuum. The reaction mixture was diluted with DCM (100 mL) and washed with 25 mL of a saturated NaHCO3 solution. The organic phase was separated and dried over Na2SO4. The crude product was purified on silica eluting with 0-15% MeOH/DCM to give product (240 mg, 0.602 mmol, 37.9% yield) as a pale yellow oil.
