2-Methyl-3-butyn-2-ol → 4-(4-amino-1-((8-methyl-2-(2-(trifluoromethyl)phenyl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methylbut-3-yn-2-ol

Participants

Reaction Steps

A suspension of 3-iodo-1-((8-methyl-2-(2-(trifluoromethyl)phenyl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.0569 g, 0.102 mmol) and copper(i) iodide (0.00387 g, 0.0203 mmol, 0.2 eq) in DMF (2 mL) was treated with 2-methyl-3-butyn-2-ol (0.0984 mL, 1.02 mmol, 10 eq), triethylamine (0.0282 mL, 0.203 mmol, 2 eq) and tetrakis(triphenylphosphine)palladium(0) (0.0117 g, 0.0102 mmol, 10 mol %) under Ar. The mixture was stirred under Ar at rt for 45 min. The mixture was concentrated under reduced pressure. The residue was purified by column chromatography on a 40 g of Redi-Sep™ column using 0 to 100% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 over 14 min as eluent to provide 4-(4-amino-1-((8-methyl-2-(2-(trifluoromethyl)phenyl)quinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methylbut-3-yn-2-ol [PI3Kδ IC50=116 nM] as a tan solid. 1H NMR (DMSO-d6) δ ppm 8.21 (1 H, s), 8.02 (1H, s), 7.87 (1 H, d, J=7.8 Hz), 7.77-7.82 (1 H, m), 7.65 (1 H, d, J=6.7 Hz), 7.57-7.62 (2 H, m), 7.51-7.57 (1 H, m), 7.26-7.32 (1 H, m), 5.76 (1 H, s), 5.44 (2 H, s), 2.60 (3 H, s), 1.46 (6 H, s). Mass Spectrum (ESI) m/e=517.2 (M+1).

Provenance & Evidence