1,2-Dichloroethane → HCID 178473725, compound

Participants

Reaction Steps

Compound E (5.0 g, 14.0 mmol) and 4-formylimidazole (4.45 g, 46.3 mmol) were dissolved in 1,2-DCE (100 mL) and acetic acid (50 mL). Sodium triacetoxyborohydride (4.45 g, 21.0 mmol) was added all at once and the mixture was stirred at room temperature for 1 h. Saturated NaHCO3 (50 mL) was added followed by ammonium hydroxide (50 mL). The mixture was stirred for 2 h, concentrated and the residue was partitioned between water (100 mL) and ethyl acetate (200 mL). The organic layer was washed with water (100 mL), brine (100 mL), dried (Na2SO4), concentrated and chromatographed (silica gel, 5.1×15 cm, 95% dichloromethane, 5% methanol) to yield the free base of Example 225 as a brown solid (4.9 g). This brown solid was further purified by preparative HPLC (YMC S-15 ODS column, 50×500 mm; solvent A, 0.1% TFA in 90% water, 10% methanol; solvent B, 0.1% TFA in 10% water, 90% methanol: 20-100% B in 60 min, flow rate 25 mL/min). Fractions containing the desired product were combined, concentrated and lyophilized. This lyophilate was dissolved in acetonitrile (50 mL) and 1N HCl (50 mL). This mixture was concentrated and lyophilized. This procedure is repeated to provide Example 226 as a yellow solid (2.3 g, 35%)

Provenance & Evidence