A solution of 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 (0.16 g, 0.40 mmol) and paraformaldehyde (neat, 0.024 g, 0.80 mmol) in MeOH (10 mL) and HOAc (1 mL) was heated at 70° C. for 14 h. The mixture was cooled to ambient temperature and sodium cyanoborohydride (0.050 g, 0.80 mmol) was added. The resulting dark solution was stirred at 70° C. for 3 h. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel (eluting with 33-60% 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-yl)-methyl-amino]-azetidine-1-carboxylic acid tert-butyl ester as yellow solid (0.081 g, 49%). LC/MS (Table 1, Method 2) Rt=1.168 min.; MS m/z: 416 [M+H]+.
