Reaction Steps
Either (5aS)-5a-(4-methoxyphenyl)-2-methyl-6-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-5a,6,7,8-tetrahydro-5H-imidazo[1,2-a]imidazo[4′,5′:4,5]pyrrolo[1,2-d]pyrazin-10(1H)-one or its regioisomer (5aS)-5a-(4-methoxyphenyl)-6-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-3-{[2-(trimethylsilyl)ethoxy]methyl}-5a,6,7,8-tetrahydro-5H-imidazo[1,2-a]imidazo[4′,5′:4,5]pyrrolo[1,2-d]pyrazin-10(3H)-one (27 mg, 0.048 mmol) similarly prepared according to steps (a), (b) and (c) was dissolved in dichloromethane (0.9 mL) and treated with trifluoro acetic acid (2.1 mL). The mixture was stirred at room temperature. After one hour the LCMS indicated complete deprotection. The mixture was then concentrated in vacuo and the residue obtained purified by flash chromatography using the biotage SP4 (0-5% MeOH gradient in EtOAc) to yield either 5a-(4-methoxyphenyl)-2-methyl-6-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5a,6,7,8-tetrahydro-5H-imidazo[1,2-a]imidazo[4′,5′:4,5]pyrrolo[1,2-d]pyrazin-10(1H)-one (2) or its regioisomer 5a-(4-methoxyphenyl)-2-methyl-6-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5a,6,7,8-tetrahydro-5H-imidazo[1,2-a]imidazo[4′,5′:4,5]pyrrolo[1,2-d]pyrazin-10(3H)-one (8.5 mg, 40% yield). ESI-MI m/z [M+H]+ 447.09. 1H NMR (400 MHz, CDCl3) δ 8.53 (br s, 1H), 8.46 (br s, 1H), 7.43 (br d, J=8.9 Hz, 2H), 6.82-6.73 (m, 2H), 6.69 (s, 1H), 6.05 (d, J=13.1 Hz, 1H), 4.46 (d, J=12.8 Hz, 1H), 4.35 (ddd, J=10.7, 8.8, 4.6 Hz, 1H), 4.00 (td, J=8.9, 5.6 Hz, 1H), 3.83 (tdd, J=13.2, 9.8, 6.6 Hz, 2H), 3.72 (s, 3H), 2.52 (s, 3H), 2.42 (d, J=0.5 Hz, 3H). The compounds in Table 1 were similarly prepared by reference to the general method(s) and/or synthetic examples.
