1H-Indole-7-carboxylic acid, 5-bromo-, methyl ester

MeI (7.81 ml_, 125 mmol) was added to a mixture of 5-bromo-1 H-indole-7-carboxylic acid (10 g, 41.7 mmol) and NaTo a solution of 5-Bromo-2, 3-dihydro-1 H-indole-7-carboxylic acid methyl ester (11.5 g, 45.1 mmol) in 10OmL THF was added MnOTo a solution of methyl 5-bromoindoline-7-carboxylate (13.5 g, 52.7 mmol) in DCM (160 mL) was added MnO2 (45.8 g, 527 mmol). The mixture was stirred at 25 °C for 48 hours. TLC (petroleum ether : ethyl acetate=10:1, Rf = 0.3) indicated that startingmaterial was consumed completely and a major new spot with higher polarity was detected. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to afford of methyl 5-bromoindole-7-carboxylate (11 g, 82percent yield) as a brown solid. 1H NMR (400 MHz DMSO) = 11.38 (s, 1H), 8.06 (s, 1H), 8.79 (s, 1H), 7.47 (d, J=6 Hz, 1H), 6.56 (d, J=3.6 Hz, 1H), 3.93 (s, 3H). ESI-MS (m/z): 253.9 (M+H)+Methyl 5-bromo-2, 3-dihydro-1 H-indole-7-carboxylate (6.5 g, 25 mmol) was dissolved in tetrahydrofuran (100 mL). Activated manganese dioxide (5 μm particle size, 22 g, 250 mmol) was added and the mixture stirred at room temperature for 16 hours. A further 22 g of activated manganese dioxide was added and the reaction stirred for 96 hours. The reaction was then filtered through celite and concentrated in vacuo to give 5.1 g (80percent) of the title compound as a beige solid.1 H NMR (400 MHz, DMSO-D6) δ ppm 3.94 (s, 3 H) 6.58 (d, J=3 Hz, 1 H) 7.48 (d, J=3 Hz550 mg (ca 1.58 mmol) of 2-amino-5-bromo-3-trimethylsilanylethynyl-benzoic acid methyl ester were dissolved in 5 ml NMP and added dropwise at 0° C. to a solution of 371 mg of potassium tert-butylate (3.31 mmol) in 5 ml NMP. After 1 h stirring at 0° C., the reaction mixture was stirred 1.5 h at rt. The reaction mixture was then treated with 20 ml water and extracted twice with diethylether. The combined organic phases were washed with brine and dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (40 g silicagel, heptane/EtOAc 100:0 the 90:10) leading to 99 mg 5-bromo-1H-indole-7-carboxylic acid methyl ester as a light brown solid (25percent). MS (EI) 253.1 (M)

Molecular Weight:254.08
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:252.97384
Monoisotopic Mass:252.97384
Topological Polar Surface Area:42.1
Heavy Atom Count:14
Complexity:234
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes