Diisopropylethylamine → (S)-N-((R)-1-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-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 with (R)-1-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)ethanamine dihydrochloride (35 mg, 0.15 mmol), (S)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (38 mg, 0.13 mmol), N-methylpyrrolidinone (200 μL) and N,N-diisopropylethylamine (93 μL, 0.53 mmol). A solution of N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (61 mg, 0.16 mmol) in N-methylpyrrolidinone (300 μL) was added and the resulting mixture was stirred at room temperature for 2 hours. The mixture was filtered and purified by reverse-phase HPLC (20-75% MeCN in 10 mM Et2NH/H2O) to afford the product as a foam (31.0 mg, 53%). 1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J=7.9 Hz, 1H), 7.53 (d, J=8.1 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.20 (s, 1H), 4.78 (app pentet, J=7.3 Hz, 1H), 4.27 (app t, J=5.2 Hz, 2H), 4.04 (t, J=6.2 Hz, 2H), 2.93-2.73 (m, 4H), 2.61-2.52 (m, 1H), 2.19-2.10 (m, 2H), 2.03-1.94 (m, 1H), 1.85-1.72 (m, 1H), 1.54 (s, 6H), 1.29 (d, J=6.9 Hz, 3H); m/z=437.4 (M+1)+.

Provenance & Evidence