Formaldehyde → HCID 86727607, compound

Participants

Reaction Steps

To a mixture of (R)-7-(2,6-difluoro-phenyl)-4-methyl-6-((3R,4R)-3-methyl-piperidin-4-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.005 g, 0.012 mmol) in AcOH (0.2 mL) and MeOH (2 mL) was added paraformaldehyde (0.004 g, 0.117 mmol) and the reaction mixture was stirred at ambient temperature for 1 h. NaBH3CN (0.002 g, 0.029 mmol) was added and the reaction mixture was stirred at ambient temperature overnight. Aqueous saturated NaHCO3 solution (30 mL) was added and the reaction mixture was extracted with EtOAc (3×50 mL). The combined organic phase was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residue was purified by preparative TLC (eluting with 20% MeOH in EtOAc) to give (R)-7-(2,6-difluoro-phenyl)-6-((3R,4R)-1,3-dimethyl-piperidin-4-yl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.0041 g, 79%). 1H NMR (400 MHz, CD3OD): 7.47-7.54 (m, 1H), 7.13 (t, J=7.91 Hz, 2H), 6.96 (s, 1H), 6.89 (s, 1H), 4.94-4.96 (m, 1H), 4.67 (m, 2H), 3.58 (m, 1H), 2.89-3.11 (m, 3H), 2.82 (s, 3H), 2.44-2.60 (m, 2H), 2.26-2.42 (m, 1H), 1.94 (m, 2H), 1.51 (d, J=6.4 Hz, 3H), 0.94 (d, J=7.4 Hz, 3H). LC/MS (Table 1, Method 4) Rt=1.656 min.; MS m/z: 441 [M+H]+. SFC (Table 2, Method 28), Rt=4.708 min.

Provenance & Evidence