4-Methylmorpholine → HCID 178462334, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (4S,5R)-3-(tert-butoxycarbonyl)-2,2,5-trimethyl-1,3-oxazolidine-4-carboxylic acid (Preparation 57, 778 mg, 3 mmol) and HOBt (551 mg, 3.60 mmol) in DMF (23 mL) was added NMM (0.33 mL, 3 mmol) and the mixture cooled to −5° C. EDCI (690 mg, 3.60 mmol) was added and the reaction stirred at −5° C. for 90 minutes. A solution of 3′,4′-diamino-2-fluorobiphenyl-4-carbonitrile (Preparation 79, 750 mg, 3.30 mmol) in DMF (7 mL) was added and the reaction was allowed to warm to room temperature for 3 days. The reaction was poured in EtOAc (120 mL), washed with 3% aqueous NaHCO3 solution (4×120 mL), brine (30 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with EtOAc:Heptane 1:1. The residue was dissolved in AcOH (7 mL) and stirred at 40° C. for 18 hours. The reaction was concentrated in vacuo and treated with saturated aqueous NaHCO3 solution (15 mL), extracted into EtOAc (2×15 mL), the organic layers combined, dried over Na2SO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with acetone:heptanes 1:3. The residue was dissolved in 4M HCl in dioxane with 1 drop of water and stirred at room temperature for 2 hours. The reaction was eluted through an SCX column washing through with MeOH followed by 3N NH3 in MeOH and the filtrate concentrated in vacuo. The residue was treated with water (1 mL) and MeOH (0.5 mL) and freeze dried to afford the title compound (125 mg, 75%).

Provenance & Evidence