Water → Ammonium Hydroxide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-{4-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-ethanol (example 192) (53 mg, 0.127 mmole) in DMF (1 mL) are added tertbutylisocyanate (16 mg, 0.26 mmole) and CuCl (13 mg, 0.13 mmole). The reaction mixture is heated at 50° C. for 24 hours. Water is added, and 1N NaOH to reach pH 9-10. The aqueous phase is extracted three times with AcOEt, and the organic phase is washed with water, brine, dried over MgSO4, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH) with a gradient from (98:2) to (9:1) then (CH2Cl2:MeOH:NH4OH) (9:9:1) to give tert-butyl-carbamic acid 2-{4-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-ethyl ester.

Provenance & Evidence