Diisopropylethylamine → (3S)-1-(1-(5-chloropyrazin-2-yl)-3,3-dimethylpiperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a solution of (3S)-1-(3,3-dimethylpiperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (0.010 g, 0.026 mmol) in DMF (1 mL) was added 2,5-dichloropyrazine (0.0078 g, 0.052 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.018 mL, 0.10 mmol) and the reaction was stirred for 3 hours at 100° C. The reaction was cooled, poured into brine and extracted into EtOAc. The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated under vacuum. Reverse phase HPLC purification of the crude material gave (3S)-1-(1-(5-chloropyrazin-2-yl)-3,3-dimethylpiperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (0.0023 g, 0.0046 mmol, 18% yield) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 1.02 (s, 3H), 1.03 (s, 3H), 1.81-1.91 (m 1H), 2.12-2.21 (m, 1H), 2.71-2.81 (m, 2H), 2.95-3.05 (m, 2H), 3.03 (m, 3H), 3.52 (dd, 2H), 3.97 (d, 1H), 4.15-4.23 (m, 2H), 4.47-4.51 (m, 1H), 5.12 (bs, 1H), 6.80 (t, 1H), 7.55 (d, 1H), 7.61 (d, 1H), 7.90 (s, 1H), 8.05 (s, 1H).

Provenance & Evidence