Aniline → HCID 86706298, compound

Participants

Reaction Conditions

Reaction Steps

To tert-butyl 6-bromo-2-(1-(tert-butoxycarbonyl)-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate 10 (50 mg, 0.108 mmole) was added cesium carbonate (70 mg, 0.216 mmole, 2 eq) and Xantphos (6.2 mg, 0.0108 mmole, 10 mole %), then a solution of 2-methoxy-4-(1-methylpiperidin-4-yloxy)aniline (30.6 mg, 0.13 mmole, 1.2 eq) in dioxane (0.7 ml). Dioxane (0.5 mL) was added and the flask flushed twice with nitrogen. Pd2(dba)3 complex (5 mg, 0.0054 mmole, 5 mole %) was added and the flask was flushed again with nitrogen (×3) and heated at 80° C. for 4 hours. The reaction was cooled and diluted with ethyl acetate (11 mL). The solution was washed with water (4 mL). The organic layer was washed with brine, dried and evaporated. The residue was applied to two 1 mm 20×20 cm silica prep tlc plates, which were eluted with 10:1 ethyl acetate:2M ammonia in methanol. The product band was recovered with ethanol containing a little 2M ammonia in methanol. This gave a gum, 60 mg, containing (by NMR) ethanol (35%) and residual aniline. This gum was applied to one 1.5 mm alumina prep tlc plate (Merck) which was eluted with 30:1 dichloromethane:2-propanol. The product band was recovered with 30% 2-propanol in dichloromethane to give a gum, 36 mg. The residue was triturated with ether to give (after removal of the ether) the title compound as a solid (22 mg, 33%). 1H-NMR (CDCl3, 500 MHz): δ 1.50 (s, 9H), 1.69 (s, 9H), 1.84-1.93 (m, 2H), 2.02-2.09 (m, 2H), 2.29-2.39 (s, 3H over m, 2H), 2.71-2.80 (m, 2H), 3.87 (s, 3H), 4.26-4.32 (m, 1H), 6.53 (dd, J=2.52, 8.83 Hz, 1H), 6.56 (d, J=0.63 Hz, 1H), 6.58 (d, J=2.52 Hz, 1H), 6.67 (s, 1H), 7.45 (s, 1H), 7.70 (d, J=8.51 Hz, 1H), 7.81 (d, J=0.63 Hz, 1H), 8.20 (d, J=0.63 Hz, 1H), 8.44 (d, J=0.95 Hz, 1H).

Provenance & Evidence