Diisopropylethylamine → (8aS)-N-(4-Chloro-2-cyclopropylpyridin-3-yl)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamide

Participants

Reaction Steps

L1 (1.0 eq.) and DIPEA (5.0 eq.) in DCM (0.1M) was slowly added to an ice cooled solution of triphosgene (0.33 eq.) in DCM (0.1M). The reaction mixture was stirred 30 min at RT and slowly added to a solution of Example 4, D2 (0.5 eq) and DIPEA (0.5 eq) in DCE (0.1M). The reaction mixture was stirred 3 h at RT, volatiles were removed under reduced pressure and the crude product was purified by preparative RP-HPLC using H2O (0.1% TFA) and MeCN (0.1% TFA) as eluents. The desired fractions were lyophilized to afford the title compound as a white powder. 1H-NMR (400 MHz, DMSO-d6, 300K) δ 8.80 (1H, br. s), 8.24 (1H, d, J=5.1 Hz), 7.34 (1H, d, J=5.1 Hz), 7.32-7.26 (2H, m), 7.25-7.17 (3H, m), 4.39 (1H, dd, J=4.1 and 13.0 Hz), 4.17-4.06 (2H, m), 3.97-3.90 (1H, m), 3.12-2.88 (3H, m), 2.72-2.65 (1H, m), 2.43-2.35 (1H, m), 2.30-2.20 (1H, m), 1.55-1.47 (1H, m), 1.45-1.38 (1H, m), 0.98-0.90 (4H, m). MS (ES) C24H24ClN5O3 requires: 465, found: 466, 468 (M+H)+.

Provenance & Evidence