Sodium Carbonate → HCID 86727506, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-[(S)-1-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-ethyl]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (Example #133, Step D, 0.08 g, 0.162 mmol), (2-fluorophenyl)boronic acid (0.027 g, 0.195 mmol) and sodium carbonate (0.034 g, 0.324 mmol) in 1,4-dioxane (2.0 mL) and water (0.5 mL) was added PdCl2(dppf)-DCM adduct (0.013 g, 0.016 mmol) and the reaction mixture was stirred at 90° C. overnight. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was partitioned between EtOAc (30 mL) and water (30 mL). The organic layer was separated and the aqueous phase was extracted with EtOAc (3×50 mL). The combined organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated in vacuo and the residue was purified by prep-TLC (eluting with 5% methanol in dichloromethane) to give 3-{(R)-1-[(R)-7-(2-fluoro-phenyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-ethyl}-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.083 g, 100%). 1H NMR (CDCl3, 400 MHz): δ 8.12 (br. s, 1H), 7.37 (m, 1H), 7.08-7.26 (m, 3H), 6.84-6.91 (m, 1H), 6.79 (m, 1H), 4.73-4.87 (m, 1H), 4.59-4.68 (m, 2H), 3.57 (m, 1H), 3.44-3.51 (m, 1H), 3.33-3.41 (m, 1H), 3.25 (m, 1H), 2.86 (m, 1H), 1.55 (d, J=6.8 Hz, 3H), 1.35-1.47 (m, 9H), 1.22-1.35 (m, 3H), 1.07-1.21 (m, 3H). LC/MS (Table 1, Method 25) Rt=0.883 min; MS (ESI): m/z 531 [M+Na]+ and 453 [M+H−56]+.

Provenance & Evidence