1,1'-Carbonyldiimidazole → 3-{4-[3-(1-Methyl-1H-benzoimidazol-2-yl)-phenyl]-piperazine-1-carbonyl}-morpholine-4-carboxylic acid tert-butyl ester

To a solution of morpholine-3,4-dicarboxylic acid-4-tert-butyl ester (0.16 g, 0.71 mmol) in acetonitrile (8 mL) was added CDI (0.16 g, 0.71 mmol) and the resulting suspension was stirred at room temperature overnight. 1-Methyl-2-(3-piperazin-1-yl-phenyl)-1H-benzoimidazole dihydrochloride (0.20 g, 0.55 mmol) (obtained as described in method C) and DIPEA (0.19 mL, 1.10 mmol) were added and the resulting solution heated at 65° C. overnight. The reaction was then cooled to room temperature, the solvent removed, the crude product was dissolved with dichloromethane (15 mL) and washed with saturated NaHCO3 solution (2×3 mL) The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (eluent: gradient from cyclohexane to cyclohexane:EtOAc 2:1) to afford 0.11 g (40%) of the title compound.

1. temperaturethe resulting solution heated at 65° C. overnight
2. temperatureThe reaction was then cooled to room temperature
3. customthe solvent removed
4. dissolutionthe crude product was dissolved with dichloromethane (15 mL)
5. washwashed with saturated NaHCO3 solution (2×3 mL) The organic layer
6. dry with materialwas dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by flash chromatography (eluent: gradient from cyclohexane to cyclohexane:EtOAc 2:1)

ORD record

ord-ee294754f091400fb7b0500efc33878d

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592463B2