Yield:379234-99-8 65%

Reaction Conditions:

dimethyl amine in acetic acid at 20; for 3 h;Under N₂;

Steps:

7.24 Preparation of gramine

Acetic acid (6 ml) was added dropwise to aqueous dimethylamine (7.0 ml, 55.7 mmol) at a rate that maintained the solution below 5° C. To this mixture was added aqueous formaldehyde (4.2 ml, 55.7 mmol) dropwise. The resulting mixture then was added to a solution of 6-cyanoindole (6.6 g, 46.4 mmol) in acetic acid (30 ml) over 15 minutes at room temperature under a nitrogen blanket. The resulting dark yellow solution was stirred at room temperature for 3 hours, followed by dilution with 2 N sodium hydroxide (30 ml), then stored at 0° C. for 12 hours. The solution was decanted, and the solvent was removed under reduced pressure to produce a white foam. The white foam was dissolved in water (200 mL), and adjusted to a basic pH with a saturated NaHCO3 solution. The resulting mixture was extracted with ethyl acetate (3×200 mL), dried over Na2SO4, and the solvent was removed under reduced pressure to yield Intermediate 24 as an off-white solid (6.24 g, 65%): 1H NMR (300 MHz, DMSO-d6): δ 11.52 (s, 1H), 7.85 (s, 1H), 7.77 (d, J=8.2 Hz, 1H), 7.54 (d, J=2.4 Hz, 1H), 7.31 (dd, J=1.5, 8.3 Hz, 1H), 3.56 (s, 2H), 2.13 (s, 6H) ppm

References:

US2003/225092,2003,A1 Location in patent:Page 17