Trifluoroacetic acid → 2-Quinoxalinecarboxamide

To the lactone from method A (100 mg, 0.27 mmol) was added neat trifluoroacetic acid (1 mL). The resulting solution was stirred for 1 h and the trifluoroacetic acid removed in vacuo. The remaining residue was solvated in methylene chloride (10 mL) and triethylamine (0.15 mL, 1.07 mmol). Quinoxalyl chloride (58 mg, 0.3 mmol) was added as a solid and the mixture stirred for 18 h. The mixture was transferred to a separatory funnel and washed with citric acid (2×10 mL), NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried (MgSO4) and the solvents filtered. The filtrate was concentrated in vacuo and the resulting residue was chromatographed on silica gel (10 g) eluting with 2:1 hexanes:ethyl acetate to provide 99 mg of the quinoxaline amide. This material was solvated in MeOH and ammonia gas was bubbled in for 5 min. The resulting solution was stirred for 16 h and the solvent removed in vacuo. The remaining residue was recrystallized (methylene chloride/methanol/Hexanes) to provide the title compound (90 mg, 72%). 1H NMR (400 MHz, CD3OD): d 9.38 (1H, s), 8.21 (1H, dd, J=4.4, 2.5 Hz), 8.14 (1H, dd, J=4.4, 2.5 Hz), 7.93 (2H, m), 7.26 (2H, d, J=6.9 Hz), 7.17 (2H, t, J=7.1 Hz), 7.09 (1H, t, J=7.3 Hz), 4.30 (1H, m), 3.75 (1H, m), 3.03-2.98 (2H, m), 2.47 (1H, m), 1.77 (1H, m), 1.56 (2H, m), 1.4 (2H, m), 1.07 (6H, s).

1. customthe trifluoroacetic acid removed in vacuo
2. stirringthe mixture stirred for 18 h
3. customThe mixture was transferred to a separatory funnel
4. washwashed with citric acid (2×10 mL), NaHCO3 (10 mL) and brine (10 mL)
5. dry with materialThe organic layer was dried (MgSO4)
6. filtrationthe solvents filtered
7. concentrationThe filtrate was concentrated in vacuo
8. customthe resulting residue was chromatographed on silica gel (10 g)
9. washeluting with 2:1 hexanes

ORD record

ord-ab658056b28b46029a2ec660076d5d0f

Source dataset

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06673801B1