1,1'-Carbonyldiimidazole → 1,3-Dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-N-(4-phenylisoxazol-5-yl)hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamide

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Reaction Steps

4-Phenylisoxazol-5-amine (2 eq) was dissolved in THF (0.1M) and treated with LiHMDS (0.1N, 2 eq), after stirring for 1 h CDI (1 eq) was added. The suspension was stirred for a further 2 h and then A5 (1 eq, 0.1 M) was added and the reaction stirred 5 h. The reaction was quenched with sat. aq. NH4Cl solution and then extracted with EtOAc. Organic layers were washed with brine, dried and concentrated under reduced pressure. The crude material 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 in 30% yield. 1H NMR (400 MHz, DMSO, 300K) δ 9.68 (1H, s), 9.00 (1H, s), 7.54 (2H, m), 7.43 (2H, m), 7.30 (3H, m), 7.23 (3H, m), 4.35 (1H, m), 4.16-4.06 (2H, m), 3.17-2.88 (3H, m), 2.69 (1H, m), 2.42-2.31 (1H, m), 1.61-1.49 (1H, m), 1.45-1.39 (1H, m). MS (ES+) C25H23N5O4 requires 457, found: 458 (M+H)+.

Provenance & Evidence