Methyl 6-bromopyridine-2-carboxylate → HCID 11951624, compound

Participants

Reaction Conditions

Reaction Steps

1-(Bromomethyl)-3-iodobenzene was used to alkylate 1-(2,2-dimethyl-propyl)-4-propyl-1H-indol-5-ol following the procedure outlined in example 1. A mixture of the above indole (3.4 g, 7.3 mmol), hexamethyldistannane (5.0 g, 15 mmol), Pd(PPh3)4 (0.80 g, 0.69 mmol), and THF (40 mL) was heated at 60° C. for 18 h under N2 and then allowed to cool to rt. The reaction mixture was diluted with water and extracted with ethyl acetate (×3). The organic extracts were dried (Na2SO4), filtered, concentrated, and purified by silica gel chromatography to give 1-(2,2-dimethylpropyl)-4-propyl-5-{[3-(trimethylstannyl)-benzyl]oxy}-1H-indole as a yellow oil. A mixture of the above stannane (0.35 g, 0.70 mmol), methyl 6-bromopyridine-2-carboxylate (0.22 g, 1.0 mmol), Pd(PPh3)4 (0.10 g, 87 μmol), and degassed toluene (10 mL) was heated at 110° C. for 24 h under N2 and then allowed to cool to rt. The reaction mixture was purified by silica gel chromatography (hexanes:ethyl acetate—1:0→2:1) to give a yellow oil. MS (ESI): 471.1 (M+H). A similar procedure as outlined in example 26 was followed for the saponification of the above ester. 1H NMR (DMSO, 500 MHz) 13.18 (br s, 1H), 8.31 (s, 1H), 8.19 (d, 1H), 8.12 (d, 1H), 8.09 (t, 1H), 8.01 (d, 1H), 7.61-7.53 (m, 2H), 7.28 (d, 1H), 7.23 (d, 1H), 7.00 (d, 1H), 6.40 (d, 1H), 5.19 (s, 2H), 3.91 (s, 2H), 2.84 (t, 2H), 1.68-1.58 (m, 2H), 0.93 (s, 9H), 0.91 (t, 3H). MS (ESI): 457.1 (M+H).

Provenance & Evidence