Triethylamine → HCID 54692325, compound

Participants

Reaction Steps

2-(4-Fluorobenzyl)-7-isopropyl-4-[2-(methylamino)ethyl]-1,6,8-trioxo-1,3,4,6,7,8-hexahydro-2H-pyrazino[1,2-c]pyrimidin-9-yl acetate (Example 67, Step 2, 37 mg, 0.08 mmol) in CH2Cl2 (1.5 mL) was treated with a large excess of reagents (70 μL MsCl, 270 μL triethylamine and 20 mg DMAP). Stirring the reaction at ambient temperature over night gave complete conversion to the sulfonamide with exchange of the 9-acetate to the 9-mesylate. The solvent was removed under a steady nitrogen stream at 50° C. and the residue dissolved in MeOH (1 mL) and treated with a solution of sodium methoxide in MeOH (25 wt %, 2.5 mL). After four days of stirring at ambient temperature, cleavage of the 9-mesylate to the 9-hydroxy was complete. The mixture was quenched by the addition of TFA and water and was then concentrated under a steady stream of nitrogen at 50° C. The crude material was purified by reverse phase preparative HPLC to afford the title compound as an off-white solid. 1H NMR (500 MHz, CDCl3) δ 11.73 (s, 1 H), 7.38-7.27 (m, 2 H), 7.09-7.05 (m, 2 H), 5.22-5.15 (m, 1 H), 4.96 (d, J=14.5 Hz, 1 H), 4.78-4.76 (m, 1 H), 4.37 (d, J=14.0 Hz, 1 H), 3.72 (dd, J=1.5, 14.0 Hz, 1 H), 3.62 (dd, J=3.8, 14.0 Hz, 1 H), 2.83 (s, 3 H), 2.80-2.66 (m, 5 H), 1.90-1.83 (m, 1 H), 1.56-1.49 (m, 1 H), 1.47 (d, J=7.0 Hz, 6 H). HRMS (APCI) M+H: calcd for (C21H28FN4O6S)+ 483.1708. found 483.1729.

Provenance & Evidence