Reaction Steps
To a solution of triphosgene (47 mg, 0.16 mmol) in EtOAc (2 mL) at 0° C. was added solution of (1S,8aS)-1-o-tolylhexahydropyrrolo[1,2-a]pyrazin-6(7H)-one (74 mg, 0.32 mmol), DMAP (4 mg, 0.032 mmol) and TEA (49 mg, 0.48 mmol) in EtOAc (2 mL). The mixture was stirred for 1.5 h, followed by addition of (R)-1-(3-ethyl-5-(trifluoromethyl)phenyl)-N-methylethanamine (111 mg, 0.48 mmol) in EtOAc (2 mL) and TEA (97 mg, 0.963 mmol). The reaction was stirred at 50° C. for 48 h and quenched with water. The resulting mixture was extracted with EtOAc and the organic layer was washed with 1 M aqueous HCl solution, dried over anhydrous Na2SO4 and then concentrated in high vacuum. The residue was purified by Prep-HPLC to give the title compound (25 mg, yield: 17%). 1H NMR (400 MHz, CDCl3) δ ppm 7.34 (s, 1H), 7.26 (d, J=7.8 Hz, 1H), 7.20 (s, 1H), 7.17 (d, J=4.8 Hz, 1H), 7.13 (dd, J=14.9, 7.3 Hz, 2H), 7.06 (s, 1H), 5.49 (q, J=6.8 Hz, 1H), 4.11 (dd, J=20.6, 11.3 Hz, 2H), 3.71 (dd, J=16.8, 7.4 Hz, 1H), 3.28 (d, J=11.9 Hz, 1H), 3.11 (t, J=12.3 Hz, 1H), 2.95 (td, J=11.8, 2.9 Hz, 1H), 2.66 (d, J=10.2 Hz, 4H), 2.61 (d, J=7.6 Hz, 1H), 2.55 (s, 3H), 2.47 (m, 1H), 2.38-2.26 (m, 1H), 1.84 (ddd, J=16.7, 13.0, 3.9 Hz, 1H), 1.67 (ddd, J=17.3, 13.1, 9.3 Hz, 1H), 1.36 (d, J=6.6 Hz, 3H), 1.21 (t, J=7.6 Hz, 3H); m/z (ES+): 488 [M+H]+.
