Formaldehyde → HCID 86727615, compound

Participants

Reaction Steps

To a solution of (R)-6-((2R,5S)-2,5-dimethyl-piperazin-1-yl)-7-(2-fluoro-phenyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one hydrochloride (0.040 g, 0.094 mmol) in AcOH (1 mL) and MeOH (10 mL) was added paraformaldehyde (0.028 g, 0.945 mmol) and the reaction mixture was stirred at ambient temperature for 1 h. NaBH3CN (0.015 g, 0.236 mmol) was added and the reaction mixture was stirred at ambient temperature overnight. Aqueous saturated NaHCO3 solution (10 mL) was added and the reaction mixture was extracted with EtOAc (3×20 mL). The combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative TLC (eluting with 20% MeOH in EtOAc) to give (R)-7-(2-fluoro-phenyl)-4-methyl-6-((2R,5S)-2,4,5-trimethyl-piperazin-1-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.011 g, 60%). 1H NMR (400 MHz, CD3OD): δ 7.33-7.41 (m, 1H), 7.18-7.29 (m, 2H), 7.14 (m, 1H), 7.06 (s, 1H), 6.93 (s, 1H), 4.58-4.69 (m, 3H), 3.18 (m, 2H), 2.96 (m, 1H), 2.71 (m, 2H), 2.59 (m, 3H), 2.27 (m, 1H), 1.48 (d, J=6.5 Hz, 3H), 1.15 (d, J=4.8 Hz, 3H), 0.75 (d, J=6.0 Hz, 3H). LC/MS (Table 1, Method 4) Rt=1.708 min.; MS m/z: 439 [M+H]+. SFC (Table 1, Method 56), Rt=2.337 min.

Provenance & Evidence