Dichloromethane → HCID 9806212, compound

Participants

Reaction Conditions

Reaction Steps

A solution of the product from Step D (0.578 g, 1.71 mmol) was stirred in 30% trifluoroacetic acid in methylene chloride for 1 h. The volatiles were removed in vacuo, and the residue dissolved in dichloroethane (5 mL). The pH was adjusted to 5-6 with N-methylmorpholine. Sodium triacetoxyborohydride (0.544 g, 2.57 mmol) and 1-(4-cyanobenzyl)imidazolyl-5-carboxaldehyde from Step I (0.361 g, 1.71 mmol) was added. The reaction was stirred overnight at 20° C. then poured into saturated sodium bicarbonate solution. The organic phase was washed with saturated brine and dried over magnesium sulfate. The crude product was purified by preparative HPLC on a 40×100 mm Waters PrepPak® reverse phase HPLC column (Delta-Pak™ C18 15 μm, 100 Å) using a gradient elution of 25% (0.1% TFA in acetonitrile), 75% (0.1% TFA in water) progressing to 45% (0.1% TFA in acetonitrile), 55% (0.1% TFA in water) over 50 min. Pure fractions were combined, concentrated, and the residue partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic layer was dried over magnesium sulfate. The purified product was converted to the hydrochloride salt with HCl in dichloromethane. The title compound was obtained as a white solid. FAB ms (m+1) 434. Anal. Calc. for C22H26F3N5O·2.0 HCl: C, 52.18; H, 5.57; N, 13.83. Found: C, 52.41; H, 5.60; N, 13.65.

Provenance & Evidence