Diisopropylethylamine → N-((R)-1-(2-Fluoro-5-methyl-4-(methylsulfonamido)phenyl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamide

Participants

Reaction Steps

A solution of N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (19.8 mg, 0.0522 mmol) and N,N-diisopropylethylamine (28 uL, 0.16 mmol) in N-methylpyrrolidinone (300 uL) was added to (R)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (15 mg, 0.052 mmol) in a 2 mL vial, and the mixture stirred at room temperature for 1 h, before a solution of (R)—N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride (18 mg, 0.063 mmol) in N-methylpyrrolidinone (200 uL) was added. After 18 h the mixture was filtered and purified by reverse-phase HPLC (30-75% MeCN in 10 mM Et2NH/H2O) to afford the amide as a solid (12.3 mg, 46%). 1H NMR (400 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.41 (app dd, J=7.7, 12.0 Hz, 1H), 7.53 (app dd, J=3.3, 8.1 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 7.07 (d, J=11.6 Hz, 1H), 5.09 (app hextet, J=7.3 Hz, 1H), 3.01 (s, 3H), 2.92-2.78 (m, 4H), 2.71-2.61 (m, 1H), 2.26 (s, 3H), 2.06-1.97 (m, 1H), 1.87-1.69 (m, 1H), 1.53 (s, 3H), 1.35 (d, J=7.1 Hz, 3H); m/z=516.3 (M+H)+.

Provenance & Evidence