Potassium Carbonate → (R)-3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a mixture of (R)-3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.5 g, 0.625 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.05 g, 0.06 mmol) and K2CO3 (0.43 g, 1.87 mmol) in dioxane (24 mL) and water (4 mL) was added 2-((E)-2-ethoxy-vinyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.123 g, 0.62 mmol) and the reaction mixture was stirred at 100° C. for 3 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo to give the crude product, which was purified by column chromatography on silica gel (eluting with 50% EtOAc in petroleum ether) to give (R)-3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.22 g, 74%) as a light yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.16 (s, 1H), 6.73 (s, 1H), 6.61 (d, J=12.4 Hz, 1H), 6.07 (s, 1H), 5.56 (d, J=12.4 Hz, 1H), 4.65 (m, 1H), 4.48 (m, 2H), 3.90 (m, 1H), 3.80 (m, 2H), 3.64 (m, 1H), 3.40 (m, 2H), 3.09-3.30 (m, 1H), 2.22 (m, 1H), 1.82 (m, 1H), 1.42 (m, 12H), 1.28 (t, J=7.2 Hz, 3H). LC/MS (Table 1, Method 2) Rt=1.100 min.; MS m/z: 472 [M+H]+. SFC (Table 1, Method 37) Rt=2.183 min.

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