To a solution of 7-(2-fluoro-phenyl)-4-methyl-6-(3-methyl-azetidin-3-ylamino)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.216 g, 0.545 mmol) in MeOH (10 mL) and acetic acid (1 mL) was added paraformaldehyde (0.05 g, 1.635 mmol) followed by NaBH3CN (0.068 g, 1.090 mmol). The mixture was stirred at ambient temperature for 30 min. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (30 mL×3). The combined organic phase was washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and evaporated in vacuo to give the residue, which was purified by chromatography on silica gel (eluting with 50% EtOAc in petroleum ether to 10% methanol in EtOAc) to give 6-(1,3-dimethyl-azetidin-3-ylamino)-7-(2-fluoro-phenyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.150 g, 67%). 1H NMR (CDCl3, 400 MHz): δ 7.37 (m, 2H), 7.24 (m, 2H), 6.78 (s, 1H), 6.02 (s, 1H), 4.78 (m, 1H), 4.55 (m, 2H), 3.90 (m, 2H), 3.80 (m, 2H), 2.75 (s, 3H), 1.59 (s, 3H), 1.48 (d, J=6.8 Hz, 3H). LC/MS (Table 1, Method 25) Rt=0.715 min.; MS m/z: 410 [M+H]+.
