1,4-Dioxane → (R)-1-(3-(ethylamino)-7-methyl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea

Participants

Reaction Conditions

Reaction Steps

An oven-dried 5 mL microwave vial was charged with (R)-1-(7-bromo-3-(ethylamino)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (100 mg, 0.198 mmol), PdOAc2 (8.5 mg, 0.038 mmol), and PCy3-BF4H (30 mg, 0.08 mmol). The reaction mixture was sealed under N2, then charged with dioxane (1.0 mL) and NMP (0.25 mL), followed by drop-wise addition of dimethylzinc (1.653 mL, 1.984 mmol, 1.2 M in toluene). The reaction was heated to 100° C. and stirred for 17 h. The reaction was quenched with TFA until gas evolution ceased and then poured into sat. aq. NaHCO3. The aqueous layer was extracted with EtOAc (×3). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (0-20% MeOH/DCM) followed by purification via mass-triggered reverse-phase HPLC. Fractions containing pure compound were filtered through a PS-HCO3 cartridge and the filtrate was concentrated in vacuo to give (R)-1-(3-(ethylamino)-7-methyl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea. MS ESI calc'd. for C18H22N6O [M+1]+ 339. found 339. 1H NMR (500 MHz, DMSO-d6) δ 8.55 (s, 1H), 7.42-7.19 (m, 5H), 5.01 (q, J=6.9 Hz, 1H), 3.36 (m, 2H), 2.29 (s, 3H), 1.53 (d, J=7.0 Hz, 3H), 1.30 (t, J=7.2 Hz, 3H).

Provenance & Evidence