Cesium carbonate → (S)-3-methyl-3-[4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a solution of 6-bromo-4-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one ((Preparation #1, Step E, 2.184 g, 5.12 mmol) and (S)-3-amino-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.977 g, 4.88 mmol) in toluene (5 mL) was added Pd(OAc)2 (0.110 g, 0.488 mmol) and dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (0.464 g, 0.976 mmol) followed by cesium carbonate (3.18 g, 9.76 mmol) and the reaction mixture was heated at reflux overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 50% EtOAc in petroleum ether) to give (S)-3-methyl-3-[4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]pyrrolidine-1-carboxylic acid tert-butyl ester (1 g, 38%). 1H NMR (400 MHz, CDCl3) δ 6.85 (m, 1H), 6.34-6.28 (m, 2H), 5.11 (m, 2H), 4.70-4.52 (m, 3H), 3.68 (m, 2H), 3.70-3.35 (m, 4H), 2.20 (m, 1H), 1.88 (m, 1H), 1.46 (m., 12H), 1.05 (m, 2H), 0.03 (s, 9H).

Provenance & Evidence