Water → HCID 86703997, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-iodo-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 133) (50 mg, 0.114 mmole) in THF (1 mL) are added potassium 4-tert-butyldimethylsilyloxybut-1-ynyltrifluoroborate (50 mg, 0.171 mmole), PdCl2(dppf)2 (8 mg, 0.011 mmole), water and Cs2CO3 (120 mg, 0.342 mmole). The flask is evacuated and filled with argon. The reaction mixture is heated at 80° C. for 24 hours. AcOEt and water are added, and the organic phase is washed with water, dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH) (98:2) to (90:10) then (CH2Cl2:MeOH:NH4OH) (9:1:0.1). The residue is dissolved in nBu4NF 1M in THF (0.5 mL) and the reaction mixture is stirred overnight at room temperature. Water is added and the aqueous phase is extracted 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:NH4OH) as eluent with a gradient from (98:2:0.1) to (96.5:3.5:0.35) and the residue is submitted to a preparative thin-layer chromatography eluting with (CH2Cl2:MeOH:NH4OH) (9:1:1) to afford 4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-but-3-yn-1-ol.

Provenance & Evidence