反应详情

(S)-1-(tert-Butoxycarbonyl)pyrrolidine-2-carboxylic acid (53.1 mg, 0.247 mmol), and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (94 mg, 0.247 mmol) were combined in dichloromethane (2 mL). After 10 minutes, (3aS,4R,6aR)-2-(3-(trifluoromethyl)phenylsulfonyl)octahydrocyclopenta[c]pyrrol-4-amine (75 mg, 0.224 mmol) from Step A of Example 254 was added. After stirring for 10 more minutes, N-ethyl-N-isopropylpropan-2-amine (0.098 mL, 0.561 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction was quenched with saturated NaHCO3 solution, extracted with 2 mL of dichloromethane, washed with 0.1 N HCl, and concentrated in vacuo. The crude material was purified using a 12 g silica gel cartridge with a gradient of 1-5% methanol (2 N ammonia)/dichloromethane over 20 minutes to give the title compound: 1H NMR (501 MHz, pyridine-d5, temperature 90° C.) δ ppm 8.29-8.30 (bs, 1H), 8.13 (d, J=7.9 Hz, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.66-7.72 (m, 1H), 7.64 (t, J=7.9 Hz, 1H), 4.29-4.32 (m, 1H), 4.06-4.10 (m, 1H), 3.68-3.71 (m, 1H), 3.46-3.51 (m, 1H), 3.34-3.42 (m, 1H), 3.26 (dd, J=9.9, 7.4 Hz, 1H), 3.06-3.17 (m, 2H), 2.55-2.57 (m, 2H), 2.09 (d, J=3.0 Hz, 1H), 1.88-1.98 (m, 3H), 1.80-1.88 (m, 1H), 1.59-1.68 (m, 1H), 1.55 (dd, J=13.2, 8.7 Hz, 1H), 1.50 (s, 9H), 1.25-1.37 (m, 1H); MS (ESI+) m/z 532 (M+H)+.

1. additionwas added
2. customThe reaction was quenched with saturated NaHCO3 solution
3. extractionextracted with 2 mL of dichloromethane
4. washwashed with 0.1 N HCl
5. concentrationconcentrated in vacuo
6. customThe crude material was purified
7. customover 20 minutes