Hydrochloric Acid → HCID 54692319, 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 hydrochloride (from Example 67, Step 2, 37 mg, 0.077 mmol) was suspended in CH2Cl2 and treated with benzoyl chloride (15 μL, 0.13 mmol), triethylamine (36 μL, 0.26 mmol) in CH2Cl2 (214 μL), and 4-dimethylaminopyridine (2.0 mg, 0.015 mmol) in CH2Cl2 (50 μL). The solution was stirred at ambient temperature for 18 h. The resulting material was suspended in EtOAc and filtered, washing with excess EtOAc. The filtrate was concentrated at 40° C. under a steady stream of nitrogen to yield a sticky solid which was dissolved in MeOH and treated with sodium methoxide in MeOH (25 wt %, 1.5 mL). The reaction was stirred for 30 min at ambient temperature and was then treated with aqueous HCl (1 M) and trifluoroacetic acid. The mixture was concentrated at 40° C. under a steady stream of nitrogen. The resulting residue was taken up in CH2Cl2, filtered, and concentrated. Purification of the remaining residue (dissolved in MeOH) by reverse phase chromatography [95:5 water (+0.1% TFA)/MeCN (+0.1% TFA) to 5:95 water (+0.1% TFA)/MeCN (+0.1% TFA)] afforded the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ 11.77 (br s, 1H), 7.47-7.30 (m, 5H), 7.29-7.22 (m, 3H), 4.41 (d, J=14.0 Hz, 1H), 3.93 (d, J=14.0 Hz, 1H), 3.77-3.73 (m, 1H), 3.65 (d, J=11.0 Hz, 1H), 2.98 (s, 3H), 2.77 (d, J=13.0 Hz, 1H), 1.87 (br s, 1H), 1.48 (d, J=6.0 Hz, 6H). HRMS (FT/ES) M+H: calcd for (C27H29FN4O5)+ 509.2195. found 509.2214.

Provenance & Evidence