2-Bromo-1,1-dimethoxyethane → 5-Methylimidazo(1,2-a)pyridin-6-amine

Participants

Reaction Conditions

Reaction Steps

2-Methyl-3-nitro-6-amino pyridine (63 mg, 0.41 mmol) was suspended in 1.3 mL EtOH containing 0.3 mL conc. HCl. 2-Bromo-1,1-dimethoxy-ethane (73 μL, 0.62 mmol) was added and the resulting mixture was refluxed for 8 h, at which point additional 2-bromo-1,1-dimethoxy-ethane (0.1 mL, 0.85 mmol) was added. The mixture was stirred at reflux overnight, cooled and diluted with CH2Cl2. The organics were washed with sat. NaHCO3 solution, dried over MgSO4 and concentrated in vacuo. The residue was dissolved in 4 mL AcOH/EtOAc (1:1) and the resulting solution was heated to 75° C. Iron powder (46 mg, 0.82 mmol, 325 Mesh) was added and the mixture was stirred for 20 min. Additional iron powder (46 mg, 0.82 mmol, 325 Mesh) was added and stirring was continued for 30 min. The mixture was cooled to room tempearture and concentrated. The resulting residue was purified by silica gel silica gel flash chomatography with 20% MeOH in CH2Cl2 to give compound 843A (51 mg, 85%) as a yellow-brown solid. HPLC: 72% at 0.18 min and 28% at 0.27 min (retention time) (YMC S5 ODS-A column 4.6×50 mm Ballistic, 10-90% aqueous methanol over 4 mincontaining 0.2% H3PO4, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 147.85 [M+H]+.

Provenance & Evidence