Sodium hydride → 2-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorobenzonitrile

Participants

Reaction Conditions

Reaction Steps

2-(1H-Indazol-5-yloxy)-5-fluorobenzonitrile (5.000 g, 19.7 mmol) was suspended in N,N-dimethylacetamide (50 mL) and sodium hydride (0.684 g, 25.7 mmol) was added portionwise at room temperature. 2-Bromo-1,1-dimethoxyethane (3.49 mL, 29.6 mmol) was added dropwise in one portion and the reaction mixture was heated to 80° C. for 18 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to afford the crude material, which was partitioned between EtOAc and saturated aqueous NH4Cl. The combined organic layers were washed with water (3×), brine and dried (MgSO4) and then concentrated under reduced pressure to afford the crude material. The crude product was purified by flash column chromatography (eluant 25% EtOAc/Hexanes) to furnish 3.88 g (57.6%) of the desired compound. The N-2 isomer was not isolated. MS (APCI+) m/z 342 (M+1) was detected. 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.54 (d, 1H, J=9 Hz), 7.36 (m, 2H), 7.16 (m, 2H), 6.82 (dd, 1H, J=4.3 Hz, J=9.3 Hz), 4.76 (t, 1H, J=5.3 Hz), 4.49 (d, 2H, J=5.3 Hz), 3.41 (s, 6H).

Provenance & Evidence