Formaldehyde → HCID 76285725, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 4-methyl-6-(3-methyl-azetidin-3-ylamino)-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.095 g, 57% purity, 0.15 mmol) and paraformaldehyde (0.015 g, 0.45 mmol) in MeOH (10 mL) and AcOH (1 mL) was heated at 80° C. for 2 h. NaBH3CN (0.019 g, 0.30 mmol) was added and the reaction mixture was stirred at 80° C. for 0.5 h. The reaction mixture was cooled to ambient temperature. The solvent was removed in vacuo and the residue was washed with aqueous saturated Na2CO3 solution (2 mL). The aqueous phase was extracted with EtOAc (4×20 mL). The combined organic layer was dried, filtered and concentrated in vacuo to give crude 6-(1,3-dimethyl-azetidin-3-ylamino)-4-methyl-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.060 g, 78% over two steps), which was used in the next step directly. LC/MS (Table 1, Method 2) Rt=0.924 min; MS m/z: 392 [M+H]+. A solution of 6-(1,3-dimethyl-azetidin-3-ylamino)-4-methyl-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.060 g, 0.15 mmol) in ammonium hydroxide (25%, 5 mL) and dioxane (5 mL) was stirred at ambient temperature for 2 h. The solvent was removed in vacuo and the residue was purified by preparative HPLC (Table 3, Method 16) to give 6-(1,3-dimethyl-azetidin-3-ylamino)-4-methyl-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one trifluoroacetic acid (0.022 g, 27%). LC/MS (Table 1, Method 4) Rt=1.722 min; MS m/z: 392 [M+H]+.

Provenance & Evidence