Ammonia → HCID 72694676, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of compound 2-iodo-4-(1-methyl piperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 2A) (80 mg, 0.19 mmoles) in DMF (0.5 mL) in a screw-capped vial under argon are added CuI (7.2 mg, 0.038 mmole), (PPh3)2PdCl2 (13.3 mg, 19 μmole), N-Boc-propargylamine (91 mg, 0.57 mmole) and Et2NH (58 μL, 0.57 mmole). The reaction mixture is heated at 50° C. overnight. Water is added and pH adjusted to 9-10 with concentrated aqueous ammonia solution. The aqueous phase is extracted three times with AcOEt. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is pre-purified by silica gel chromatography using (CH2Cl2:MeOH) as eluent with a gradient from (95:5) to (90:10) and the residue is submitted to a preparative thin-layer chromatography eluting with (CH2Cl2:MeOH:NH4OH) (9:1:1) to afford {3-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-prop-2-ynyl}-carbamic acid tert-butyl ester.

Provenance & Evidence