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

Participants

Reaction Steps

A 4-mL vial was charged with (R)—N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride (95 mg, 0.34 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (130 mg, 0.34 mmol). A solution of 2-(2-hydroxypropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (66 mg, 0.28 mmol) and N,N-diisopropylethylamine (290 μL, 1.7 mmol) in N-methylpyrrolidinone (850 μL) was added and the mixture stirred at room temperature for 1 hour. The reaction was quenched with water (100 μL), filtered and purified by reverse-phase HPLC (10-75% MeCN in 10 mM Et2NH/H2O) to afford the amide as a light yellow solid (70 mg, 54%). Additional purification by silica chromatography was performed (0-100% EtOAc in hexanes) to obtain a white solid (45 mg, 35%). m/z=464.6 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 9.19 (br s, 1H), 8.41 (app dd J=7.8 Hz, J=11.0 Hz, 1H), 7.45 (app dd, J=3.0 Hz, J=8.0 Hz, 1H), 7.36 (app dd, J=1.5 Hz, J=8.0 Hz, 1H), 7.23 (d, J=8.5 Hz, 1H), 7.07 (d, J=11.5 Hz, 1H), 5.17-5.04 (m, 2H) 3.02 (s, 3H), 2.92-2.73 (m, 4H), 2.68-2.57 (m, 1H), 2.26 (s, 3H), 2.09-1.96 (m, 1H), 1.88-1.66 (m, 1H), 1.39 (s, 3H), 1.39 (s, 3H), 1.35 (d, J=7.0 Hz, 3H).

Provenance & Evidence