Thionyl Chloride → 2-(2-adamantyl)-N-(2-isopropyl-4-oxoquinazolin-3(4H)-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

Thionyl chloride (1.72 mL, 23.5 mmol) was added to adamant-2-yl acetic acid (241 mg, 1.24 mmol, prepared as described in J. Med. Chem, (2007), 50(1), 149-164) in a 25 mL round-bottom flask with stir bar. The resulting solution was heated at 80° C. for 1 hour, and then concentrated under vacuum. The residue was taken up in CH2Cl2 (3 mL) and concentrated under vacuum. This process was repeated twice more to ensure removal of excess thionyl chloride. The residue was taken up in fresh CH2Cl2 (2 mL) and 3-amino-2-isopropyl-4(3H)-quinazolinone (252 mg, 1.24 mmol) was added. The mixture was stirred at 20-25° C. After 18 hours, diisopropylethylamine (0.40 mL) was added and the solution was stirred for 1 hour longer, and then concentrated under vacuum. The residue was purified by flash chromatography (silica gel, eluted with hexanes-EtOAc, 90:10-70:30). Unreacted quinazolinone (80 mg, 31% recovered) eluted first, followed closely by a second fraction from which crystals precipitated on standing at room temperature for 1 hour. The crystals were collected by filtration and dried at 50° C. under vacuum to provide the title compound (102 mg, 22% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.32 (2 d, J=6.7 Hz, 6H), 1.58-1.96 (m, 14H), 2.41 (br. t, J=7.3 Hz, 1H), 2.64 (d, J=7.5 Hz, 2H), 3.16 (hept, J=6.7 Hz, 1H), 7.43 (td, J=7.3, 1.2 Hz, 1H), 7.68 (s, 1H), 7.69 (d, J=8.7 Hz, 1H), 7.75 (t, J=7.5 Hz, 1H), 8.21 ppm (d, J=7.5 Hz, 1H); MS (DCI) m/z 380 (M+H)+; Elemental Analysis calculated for C23H29N3O2.0.3H2O: C, 71.77; H, 7.75; N, 10.92. Found: C, 71.70; H, 7.68; N, 10.76.

Provenance & Evidence