Benzene → Ethyl 6-cyclopropyl-1-{[4-(methyloxy)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-{[4-(methyloxy)phenyl]methyl}-1H-pyrazol-5-amine (3 g, 14.76 mmol), ethyl 4-cyclopropyl-2,4-dioxobutanoate (2.72 g, 14.76 mmol) and benzene (50 mL) were heated at 63° C. for 16 h. The solvent was removed under reduced pressure. The crude residue was purified via silica gel chromatography (eluent: 0 to 25% EtOAc:Hex) to afford 2.56 g of the desired cyclized product and 1.71 g of the uncyclized adduct. The uncyclized adduct was dissolved in 25 mL of AcOH and heated to reflux for 16 hours. The solvent was removed under reduced pressure and the residue purified via silica gel chromatography (eluent: 0 to 25% EtOAc:Hex) to afford an additional 1.15 g of the desired cyclized product (combined yield=71%). LCMS E-S (M+H)=352.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.07-1.13 (m, 4 H) 1.38 (t, J=7.07 Hz, 3 H) 2.39 (s, 1 H) 3.67 (s, 3 H) 4.41 (q, J=7.07 Hz, 2 H) 5.51 (s, 2 H) 6.84 (d, J=8.84 Hz, 2 H) 7.21 (d, J=8.59 Hz, 2 H) 7.64 (s, 1 H) 8.23 (s, 1 H).

Provenance & Evidence