Oxalyl chloride → 4-Cyano-1H-pyrrole-2-carboxylic acid [4-methyl-6'-(4-methyl-piperazin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-3'-yl]-amide

Participants

Reaction Steps

A flask was charged with 4-cyano-pyrrole-2-carboxylic acid (as prepared in Example 2, 200 mg, 1.43 mmol), dichloromethane (30 ml), DMF (150 μL), and oxalyl chloride (275 μL, 1.60 mmol) and the mixture was stirred for 20 min at RT. Toluene (10 mL) was then added and the solvents were removed in vacuo. To the resulting acid chloride, dichloromethane (30 mL), DIEA (750 μL, 4.30 mmol), and 4-methyl-6′-(4-methyl-piperazin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-3′-ylamine (as prepared in Example 55, step (c), 385 mg, 1.33 mmol) were added and the mixture was stirred at RT for 4 days. The mixture was poured into saturated aq sodium bicarbonate (100 mL), and extracted with dichloromethane (2×25 mL) and the solvents were removed in vacuo. Purification of the resulting residue by silica gel preparative TLC eluting with 10% methanol in dichloromethane, then repurification by alumina preparative TLC eluting with dichloromethane-acetonitrile-methanol (7:2.5:0.5) yielded 38 mg (7%) of the title compound as a green solid. 1H-NMR (400 MHz, CDCl3): δ 11.32 (br s, 1H), 8.33 (d, 1H, J=8.8 Hz), 7.44 (s, 1H), 6.87 (s, 1H), 6.39 (d, 1H, J=8.8 Hz), 3.54 (m, 4H), 3.18-3.15 (m, 2H), 2.84 (m, 2H), 2.56 (m, 4H), 2.38 (s, 3H), 1.82-1.79 (m, 2H), 1.56 (m, 1H), 1.40-1.33 (m, 2H) 1.06 (d, 3H, J=6.5 Hz). LC-MS (ESI, m/z): Calcd. for C22H30N7O, 408.2 (M+H); found: 408.2.

Provenance & Evidence