N,1-dimethylindole-2-carboxamide → methyl((1-methyl-1H-indol-2-yl)methyl)amine

A 3-liter 3-necked roundbottom flask equipped with overhead stirring was charged with N,1-dimethyl-1H-indole-2-carboxamide (23.45 g, 124.58 mmole) and anhydrous THF (170 mL). The solution was stirred while a solution of LiAlH4 in THF (1.0 M, 250 mL, 250 mmole) was added via syringe. Gas was evolved during the addition of the first 50 mL of LiAlH4 solution. When the addition was complete, the resulting light yellow solution was heated at gentle reflux. After 23 hr, the reaction was cooled in ice and quenched by the sequential dropwise addition of H2O (9.5 mL), 15% NaOH (9.5 mL), and H2O (28.5 mL). The mixture was stirred for 15 min, then was filtered through Celite®, and the filter pad was washed thoroughly with THF. The filtrate was concentrated and the residue was flash chromatographed on silica gel (10% MeOH/CHCl3 containing 0.5% conc. NH4OH). The title compound (20.17 g, 93%) was obtained as a light yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.56 (d, J=7.8 Hz, 1 H), 7.02-7.35 (m, 3 H), 6.38 (s, 1 H), 3.88 (s, 2 H), 3.75 (s, 3 H), 2.49 (s, 3 H).

1. customA 3-liter 3-necked roundbottom flask equipped
2. additionwas added via syringe
3. additionWhen the addition
4. temperaturethe resulting light yellow solution was heated at gentle reflux
5. temperaturethe reaction was cooled in ice
6. customquenched by the sequential dropwise addition of H2O (9.5 mL), 15% NaOH (9.5 mL), and H2O (28.5 mL)
7. stirringThe mixture was stirred for 15 min
8. filtrationwas filtered through Celite®
9. washthe filter pad was washed thoroughly with THF
10. concentrationThe filtrate was concentrated
11. customchromatographed on silica gel (10% MeOH/CHCl3 containing 0.5% conc. NH4OH)

ORD record

ord-23ec2ee3ae644a629d2923327b731775

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07741339B2