1,1'-Carbonyldiimidazole → N-[2-(4-(4-hydroxy-1-adamantylcarbonylamino)-1-piperidinyl)ethyl]-1-(2-propyl)-1H-indazole-3-carboxamide oxalate

Participants

Reaction Steps

A mixture of 0.50 g (2.55 mmol) of 4-hydroxy-1-adamantylcarboxylic acid and 0.44 g (2.71 mmol) of 1,1'-carbonyldiimidazole in 10 mL of dimethylformamide was stirred for 2 hours at ambient temperature. To this solution was dropwise added 0.90 g (2.75 mmol) of the product of Example 23 in 7 mL of dimethylformamide. The reaction was stirred for 18 hours and then concentrated in vacuo, diluted with dichloromethane and solids removed by filtration. The crude product was purified by chromatography (silica, 9:1 dichloromethane-methanol) to provide 0.71 g (55%) of the desired product as a foam. Further treatment of 500 mg of the product with 88 mg of oxalic acid in 15 mL of ethanol provided, upon concentration of the solution, 580 mg of the oxalate salt (LSN343032). 1H NMR (300 MHz, DMSO-d6) d 8.47 (t, 1H), 8.11 (d, 1H), 7.75 (d, 1H), 7.40 (t, 1H), 7.28 (d, 1H), 7.21 (t, 1H), 6.3 (br s, 3H), 5.04 (m, 1H), 3.74 (m, 1H), 3.59 (m, 3H), 3.40 (m, 2H), 3.13 (m, 2H), 2.95 (m, 2H), 1.95 (d, 2H), 1.69 (m, 13H), 1.47 (d, 6H), 1.25 (d, 2H).

Provenance & Evidence