反应详情

A 100 mL round-bottomed flask was charged with 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (300.0 mg, 0.6119 mmol), 1-methyl-2-oxopyrrolidine-3-carboxylic acid (87.59 mg, 0.6119 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (351.9 mg, 1.836 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (248.0 mg, 1.836 mmol), N-ethyl-N-isopropylpropan-2-amine (395.4 mg, 3.060 mmol) and THF (50 mL). The reaction mixture was stirred at ambient temperature overnight, and then partitioned between EtOAc and H2O. The phases were separated, and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (0.360 g, 95.6%). LRMS (APCI pos): m/e 616 (M+1). 1H NMR (400 MHz, CDCl3) δ 10.04 (s, 1H), 8.31 (d, 1H), 7.79 (dd, 1H), 7.36 (d, 2H), 7.29 (m, 1H), 7.20 (t, 1H), 6.83 (m, 2H), 6.20 (d, 1H), 5.61 (s, 2H), 3.78 (s, 3H), 3.42-3.50 (m, 3H), 2.94 (s, 3H), 2.50-2.61 (m, 1H), 2.35-2.48 (m, 1H).

1. custompartitioned between EtOAc and H2O
2. customThe phases were separated
3. extractionthe aqueous phase was re-extracted with EtOAc
4. dry with materialThe combined organic layers were dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customto yield a crude product
8. customThe crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1