2-Bromopropane → Methyl 6-bromo-2-(propan-2-yl)-2H-indazole-4-carboxylate

Participants

Reaction Steps

To a cooled (0° C.) solution of methyl 6-bromo-1H-indazole-4-carboxylate (1.25 g, 4.90 mmol) in N,N-dimethylformamide (25 mL) was added sodium hydride (0.216 g, 5.39 mmol). The reaction mixture was stirred for 15 min, then 2-bromopropane (0.920 mL, 9.80 mmol) was added and the reaction allowed to warm to RT. The reaction was maintained at RT overnight. The contents were concentrated to about ½ volume, then poured into saturated NH4Cl (200 mL) with stirring. The contents were extracted with ether (2×) and the combined organics washed with brine, dried (MgSO4), filtered, and concentrated to give an orange residue (1.55 g crude). Purification by silica gel chromatography (eluent: 5-25% ethyl acetate in hexanes) gave methyl 6-bromo-1-(1-methylethyl)-1H-indazole-4-carboxylate (0.60 g, 40% yield) and methyl 6-bromo-2-(1-methylethyl)-2H-indazole-4-carboxylate (0.65 g, 43% yield). Both products were isolated and methyl 6-bromo-1-(1-methylethyl)-1H-indazole-4-carboxylate was taken on to the next step. Data for 1-alkylated isomer: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.48 (s, 1H) 8.02 (d, J=1.52 Hz, 1H) 7.85 (s, 1H) 4.83 (dt, J=13.33, 6.60 Hz, 1H) 4.04 (s, 3H) 1.63 (s, 3H) 1.61 (s, 3H); LC-MS(ES) [M+H]+ 297.5/299.5. Data for 2-alkylated isomer: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.72 (s, 1H), 8.25 (s, 1H), 7.80 (d, J=1.5 Hz, 1H), 4.96 (m, 1H), 3.95 (s, 3H), 1.57 (d, J=6.6 Hz, 6H); LC-MS(ES) [M+H]+ 297.5/299.5.

Provenance & Evidence