1-Hydroxybenzotriazole → N-(4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-methyl-2-oxopyrrolidine-3-carboxamide

Participants

Reaction Steps

A 100 mL round-bottomed flask was charged with 4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (15.0 mg, 0.040 mmol; obtained from Example 5, Step D), 1-methyl-2-oxopyrrolidine-3-carboxylic acid (28.4 mg, 0.20 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (38.0 mg, 0.20 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (26.8 mg, 0.20 mmol), N-ethyl-N-isopropylpropan-2-amine (0.035 mL, 0.20 mmol) and CH2Cl2 (10 mL). The reaction mixture was stirred at room temperature until LC-MS showed that the starting material was consumed. Water (10 mL) was added, and the aqueous layer was extracted with CH2Cl2 (3×50 mL). The combined organic layers were dried (Na2SO4) and concentrated, and the resulting residue was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford the desired product (14.8 mg, 74.1%). LRMS (APCI neg) m/e 502 (M−1). 1H NMR (400 MHz, CDCl3) δ 10.03 (s, 1H), 8.25 (d, J=5.2 Hz, 1H), 7.78 (dd, J=12.4, 2.4 Hz, 1H), 7.31 (d, J=8.8 Hz, 2H), 7.25-7.34 (m, 1H), 7.18 (m, 1H), 6.82 (d, J=8.8 Hz, 2H), 6.14 (m, 1H), 5.56 (s, 2H), 3.78 (s, 3H), 3.38-3.49 (m, 3H), 2.88 (s, 3H), 2.71 (s, 3H), 2.36-2.48 (m, 1H), 2.22-2.31 (m, 1H).

Provenance & Evidence