Formaldehyde → HCID 86727600, compound

To a solution of (R)-7-bromo-4-methyl-6-((3R,4R)-3-methyl-piperidin-4-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (2.2 g, 5.59 mmol) in AcOH (10 mL) and MeOH (100 mL) was added paraformaldehyde (0.839 g, 28.0 mmol). The reaction mixture was stirred at ambient temperature for 1 h. NaBH3CN (0.557 g, 14.0 mmol) was added and the resulting 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 concentrated in vacuo. The residue was purified by a reverse-phase preparatory HPLC (Table 3, Method 35) to give (R)-7-bromo-6-((3R,4R)-1,3-dimethyl-piperidin-4-yl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (1.8 g, 79%). 1H NMR (400 MHz, CD3OD) δ 7.22 (s, 1H), 6.86 (s, 1H), 4.87-4.91 (m, 1H), 4.58 (d, J=13.2 Hz, 2H), 3.15 (m, 1H), 3.04 (m, 1H), 2.84 (m, 1H), 2.23-2.39 (m, 6H), 2.07-2.18 (m, 1H), 1.55 (m, 1H), 1.43 (d, J=6.5 Hz, 3H), 0.83 (d, J=7.0 Hz, 3H). LC/MS (Table 1, Method 25) Rt=0.681 min.; MS m/z: 407 [M+H]+& 409 [M+H+2]+.

1. stirringthe resulting mixture was stirred at ambient temperature overnight
2. extractionthe reaction mixture was extracted with EtOAc (3×50 mL)
3. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by a reverse-phase preparatory HPLC (Table 3, Method 35)

ORD record

ord-cc728afc87b44aaca18189e94bdb0076

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115151B2