Indole-6-carboxaldehyde

Crystalline Solid

Preparation LIX N-[tert-butoxycarbonyl] 2-(1H-Indol-6-yl)ethylamine [0382] Indole-6-carboxaldehyde [0383] To a solution of 6-cyanoindole (15.0 g) and sodium hypophosphite (90 g) in water (326 mL), acetic acid (326 mL), and pyridine (652 mL) was added Raney Nickel catalyst and the mixture stirred at 45° C. for 45 minutes. The mixture was filtered through Celite and the filtrate extracted with ethyl acetate (3.x.500 mL). The extracts were dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was crystallized from a mixture of dichloromethane and hexanes to provide 13.6 g (89percent) of the title compound. [0384] MS (EI, m/z) C9H2NO (M+1) 145.9 [0385] 6-(2-Nitrovinyl)-1H-indole [0386] A mixture of indole-6-carboxaldehyde (2.8 g), nitromethane (30 mL) and ammonium acetate (0.560 g) was stirred at 100° C. for 30 minutes. The excess nitromethane was removed under reduced pressure and the residue washed with water, dissolved in ethyl acetate (500 mL), dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure to a volume of about 50 mL. This solution was then diluted with petroleum ether and the resulting suspension filtered and dried to provide 3.3 g (91percent) of the desired compound. To a solution of 6-(2-Nitrovinyl)-1H-indole (1.0 g) in tetrahydrofuran (100 mL) was added portionwise lithium aluminum hydride (0.95 g) and the resulting mixture stirred at reflux for 1 hour. The reaction mixture was treated sequentially with water (0.95 mL), 15percent sodium hydroxide (0.95 mL), and water (2.85 mL). The resulting suspension was filtered and the filtrate diluted with ethyl acetate (200 mL), washed with saturated aqueous sodium bicarbonate (100 mL), saturated aqueous sodium chloride, dried over sodium sulfate, filtered and the filtrate concentrated under reduced pressure. The residue was subjected to silica gel chromatography. Fractions containing product were combined and concentrated under reduced pressure to provide 0.525 g (62percent) of the desired compound. [0390] MS (EI, m/z) C10H12N2 (M+1) 160.9 [0391] Nitrogen Protection [0392] To a solution of 2-(1H-Indol-6-yl)ethylamine (0.50 g) in acetonitrile (25 mL) was added dimethylaminopyridine followed by di-tert-butyl dicarbonate (45 mg). After stirring at room temperature for 24 hours, the mixture was diluted with ethyl acetate (500 mL), washed with saturated aqueous sodium bicarbonate (200 mL), water (2.x.200 mL), saturated aqueous sodium chloride, dried over sodium sulfate, filtered and the filtrate concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 20-40percent ethyl acetate in hexanes. Fractions containing product were combined and concentrated under reduced pressure to provide 0.42 g (52percent) of the title compound. [0393] MS (EI, m/z) C15H20N2O2 (M-1) 258.9b. Dess-Martin periodinane (1.53 g, 2.6 mmol) was dissolved into methylene chloride (15 mL). Indol-6-yl-methanol (500 mg, 3.4 mmol) in methylene chloride (12 mL) was added and the mixture was stirred for 1 hr. Sodium hydroxide (5 mL of 1 N solution) was added and the reaction was stirred for 15 min. The organic layer was separated and washed with H20 (5 mL), brine (5 mL), dried over MGS04 and concentrated to afford the title compound as a brown solid (275 mg, 56percent). TH NMR (300 MHz, DMSO-D6) 8 11.7 (s, 1H), 9.98 (s, 1H), 7.97 (s, 1H), 7.70-7. 65 (m, 2H), 7.52 (dd, J= 8.2, 1.4 Hz, 1H), 6.57-6. 5 (m, 1H).

Reactant in preparation of analogs of botulinum neurotoxin serotype A protease inhibitors 1 Reactant in synthesis of stilbene-based antitumor agents 2 Reactant in acid-catalyzed preparation of aromatic gem-dihalides from aldehydes and acid halides.

Molecular Weight:145.16
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:145.052763847
Monoisotopic Mass:145.052763847
Topological Polar Surface Area:32.9
Heavy Atom Count:11
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes