Diisopropylethylamine → (S)-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 2 ml, vial was charged with (R)—N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride (51 mg, 0.18 mmol), (S)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (47 mg, 0.16 mmol) and N,N-diisopropylethylamine (110 uL, 0.65 mmol) and N-methylpyrrolidinone (0.8 mL). A solution of N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (75 mg, 0.20 mmol) in N-methylpyrrolidinone (0.4 mL) was added and the resulting mixture was stirred at room temperature. After 30 min the mixture was filtered and purified by reverse-phase HPLC (10-75% MeCN in 10 mM Et2NH/H2O) to afford the amide as a solid (72 mg, 85%). The sample was dissolved in hot 2/3 IPA/hexane (5 mL). 1.2 mL injections were separated on a ChiralPak AD-H 5 um, 250×20 mm column, eluting with 85/15/0.03 hexane/IPA/Et2NH at 20 mL/min. Peaks eluted at 7.5 and 8.7 min, with UV monitoring at 254 and 230 nm. The major isomer, eluting at 8.7 min was concentrated to afford the amide as fine plates (47 mg, 56%). 1H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 8.41 (d, J=7.6 Hz, 1H), 7.53 (d, J=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 pentet, J=7.2 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), 1.82-1.69 (m, 1H), 1.53 (s, 3H), 1.35 (d, J=7.1 Hz, 3H); m/z=516.2 (M+H)+.

Provenance & Evidence