4-Methylmorpholine → HCID 20814055, compound

Participants

Reaction Steps

To a cooled (0° C.) solution of 2-(3-cyclopropyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-ylmethyl)-1-(3-methyl-butyl)-1H-benzoimidazole-5-carboxylic acid (77 mg, 0.17 mmol) and N-methyl morpholine (23 μL, 0.21 mmol) in DCM (3 mL) was added isobutyl chloroformate (27 μL, 0.21 mmol. The mixture was allowed to warm to room temperature and stirred for 2 hrs. After concentration and trituration with ethyl acetate the solid was removed by filtration and the filtrate concentrated in vacuo. The residue containing the mixed anhydride was dissolved in THF (3 mL) and added to a stirred and cooled (0° C.) solution of sodium borohydride (65 mg, 1.7 mmol) in water. The mixture was allowed to warm to room temperature and stirred for 3 hrs., followed by quenching with satd. Na/K tartrate and stirring overnight. The mixture was extracted with ethyl acetate (3×10 mL), the combined organic phases washed with brine and dried (MgSO4). Purification by flash chromatography (eluent 2%, 5% methanol in DCM) afforded 3-cyclopropyl-1-[5-hydroxymethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-1H-quinazoline-2,4-dione (39 mg, 52%) as a white solid.

Provenance & Evidence