Sodium Carbonate → 7-(2,6-Dimethyl-pyridin-3-yl)-3-[2-((2R)-2-methyl-pyrrolidin-1-yl)-ethyl]-cinnoline

Participants

Reaction Conditions

Reaction Steps

A mixture of the product from Example 169C (0.100 g, 0.328 mmol), 2,6-dimethyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (0.077 g, 0.328 mmol), Pd(PPh3)2Cl2 (0.012 g, 0.017 mmol), and 1 M Na2CO3 (0.820 mL, 0.820 mmol) in de-gassed isopropanol/toluene (5 mL, 1:1) was heated to 90° C. under a dry nitrogen atmosphere for 24 hours. After cooling, the reaction mixture was filtered, diluted with 20 mL water, extracted twice with 25 mL dichloromethane, and concentrated under reduced pressure. Next, (2R)-2-methylpyrrolidine (L)-tartrate (0.100 g, 0.425 mmol) was partitioned between toluene (0.5 mL) and 5M NaOH/brine (1:1, 1 mL total). The toluene phase (0.5 mL) was subsequently added to a solution of the above crude material in acetonitrile (3 mL) and the resulting mixture was heated to 85° C. in a sealed tube for 48 hours. Upon cooling, the mixture was concentrated under reduced pressure and purified by column chromatography (100% dichloromethane to 95:5 dichloromethane/methanol) to provide the title compound. 1H NMR (CD3OD, 300 MHz) δ 8.38 (m, 1H), 8.19 (s, 1H), 8.06 (d, J=9 Hz, 1H), 7.84 (dd, J=3, 9 Hz, 1H), 7.76 (d, J=9 Hz, 1H), 7.27 (d, J=9 Hz, 1H), 3.52-3.28 (m, 4H), 2.78-2.62 (m, 2H), 2.59 (s, 3H), 2.52 (s, 3H), 2.46-2.39 (m, 1H), 2.08-1.98 (m, 1H), 1.86-1.78 (m, 2H), 1.56-1.42 (m, 1H), 1.18 (d, J=6 Hz, 3H). MS (ESI) [M+H]+ at 347.

Provenance & Evidence