Diisopropylethylamine → N-((R)-1-(1H-indazol-5-yl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamide

Participants

Reaction Steps

A 2 mL vial was charged sequentially with a solution of (R)-1-(1H-indazol-5-yl)ethanamine dihydrochloride (34 mg, 0.15 mmol) in NMP (0.2 mL, 2 mmol), a solution of (R)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (38 mg, 0.13 mmol) and N,N-diisopropylethylamine (93 μL, 0.53 mmol) in NMP (0.1 mL). A solution of N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (61 mg, 0.16 mmol) in NMP (0.3 mL) was added to the resulting mixture and the solution stirred at room temperature. After 30 min the mixture was filtered and purified by reverse-phase HPLC (20-75% MeCN in 10 mM Et2NH/H2O) to afford the amide as a solid (44 mg, 76%). 1H NMR (400 MHz, DMSO-d6) δ 12.98 (br s, 1H), 8.38 (d, J=8.1 Hz, 1H), 8.04 (d, J=0.4 Hz, 1H), 7.66 (s, 1H), 7.50 (t, J=8.1 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 5.06 (app pentet, J=7.3 Hz, 1H), 2.94-2.76 (m, 4H), 2.68-2.57 (m, 1H), 2.11-2.03 (m, 1H), 1.90-1.78 (m, 1H), 1.54 (s, 6H), 1.43 (d, J=7.0 Hz, 3H); m/z=431.3 (M+1)+.

Provenance & Evidence