Ammonia → 4-(1-methylpiperidin-4-yloxy)-2-phenylethynyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

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Reaction Conditions

Reaction Steps

To a solution of compound 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 2A) (100 mg, 0.24 mmoles) in ACN (600 μL) in a screw-capped vial under argon are added CuI (9 mg, 0.048 mmole), Pd(PPh3)4 (28 mg, 24 μmoles), phenylacetylene (109 μL, 0.96 mmole) and NEt3 (600 μL). The reaction mixture is heated at 80° C. overnight. Water is added and pH adjusted to 9-10 with concentrated aqueous ammonia solution. The aqueous phase is extracted three times with CH2Cl2. 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:NH4OH) as eluent with a gradient from (98:2:0.2) to (95:5:0.5) and the residue is submitted to a preparative thin-layer chromatography eluting with (CH2Cl2:MeOH:NH4OH) (9:1:1) to afford 4-(1-methylpiperidin-4-yloxy)-2-phenylethynyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene.

Provenance & Evidence