4-Methylbenzylamine → 6-Methylisoquinolin-3-amine

Temperature

70 °C

To a solution of methyl 2,2-diethoxyacetimidate (1.1 g, 6.82 mmol) in methanol (8 mL) was added p-tolylmethanamine (0.788 g, 6.50 mmol) dropwise at ambient temperature. The reaction flask was then placed into a preheated oil-bath and stirred at 70° C. for 16 h, then removed and allowed cooled. The volatiles were removed under reduced pressure and the crude material was added dropwise to sulfuric acid (5 mL) at ambient temperature. The reaction mixture was stirred for 72 h, then the flask was placed into an ice-water bath, diluted with water (50 mL), and slowly neutralized to pH=10 with sodium hydroxide (10 N). As the reaction mixture became basic, a grey precipitate formed. This precipitate was filtered, washed with water, and dried to afford 6-methylisoquinolin-3-amine (0.65 g, 63%), as a grey powder. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.73 (s, 1H), 7.69 (d, J=8.28 Hz, 1H), 7.29 (s, 1H), 7.00 (d, J=8.28 Hz, 1H), 5.81 (s, 1H), 2.40 (s, 3H). MS (LC/MS) R.T.=1.37; [M+H]+=159.10.

1. customThe reaction flask was then placed into a preheated oil-bath
2. customremoved
3. temperatureallowed cooled
4. customThe volatiles were removed under reduced pressure
5. additionthe crude material was added dropwise to sulfuric acid (5 mL) at ambient temperature
6. stirringThe reaction mixture was stirred for 72 h
7. customthe flask was placed into an ice-water bath
8. additiondiluted with water (50 mL)
9. customa grey precipitate formed
10. filtrationThis precipitate was filtered
11. washwashed with water
12. customdried

ORD record

ord-28344fa472fc45718fcc404ff05661df

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863291B2