A solution of 6-amino-4,7-dimethyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (1.1 g, 4.5 mmol) and 3-oxo-azetidine-1-carboxylic acid tert-butyl ester (1.53 g, 8.9 mmol) in methanol (45 mL) and acetic acid (5 mL) was stirred at rt for 2 h. Sodium cyanoborohydride (0.563 g, 8.9 mmol) was added and the resulting dark solution was stirred at rt for 14 h. The solvent was removed in vacuo to give the crude product, which was purified by column chromatography on silica gel (eluting with 33% EtOAc in petroleum ether) to give 3-(4,7-dimethyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (racemate, 0.580 g, 1.45 mmol, 32%) as an off-white powder. The racemate was further separated by chiral SFC (Table 2, Method 3) to give two enantiomers: 3-(4(R),7-dimethyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (enantiomer 1, SFC (Table 1, Method 8), Rt=3.090 min, 0.250 g, 14%) and 3-(4(S),7-dimethyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (enantiomer 2, SFC (Table 1, Method 8), Rt=4.151 min, 0.240 g, 13%). LC/MS (Table 1, Method 2) Rt=1.065 min.; MS m/z: 424 [M+23]+.
