6-methyl-5-nitroisoquinolin-1(2H)-one → 5-amino-6-methylisoquinolin-1(2H)-one

A suspension of 6-methyl-5-nitroisoquinolin-1(2H)-one (40 g, 196 mmol) in glacial acetic acid (1 L) was purged with N2. The suspension was treated with 10% Pd/C (10 g) and the reaction vessel was purged with H2. The mixture was stirred at room temperature under H2 (1 atm) until starting material consumed, approximately 100 h. The reaction mixture was purged with N2, then filtered through a pad of Celite. The pad was washed with MeOH (400 mL) and the combined filtrate was treated with water (80 mL) and concentrated in vacuo to ˜200 mL. The dark mixture was diluted with 200 mL MeOH and added in a thin stream to ice water (1.5 L) stirred in a large beaker. The resulting fine precipitate was collected by suction filtration. The greenish-grey powder was suspended in water (500 mL) and satd NaHCO3 (100 mL) and sonicated for 1 min. The solid was collected by suction filtration, washed with water (2×100 mL), Et2O (100 mL), and air-dried overnight to afford 28 g as a grey powder. The powder was dissolved in hot DMF (200 mL) and treated with decolorizing carbon (˜10 g). The hot suspension was filtered through Celite. The filter cake was washed with MeOH (200 mL) and the filtrate was concentrated in vacuo to ˜200 mL. The dark brown solution was added to water (1.2 L) to afford a fine crystalline precipitate. The solid was collected by suction filtration on a medium-sintered glass frit and washed with water (500 mL). A second crop precipitated in the filtrate and was collected by suction filtration, washed with water (100 mL) and added to the first crop. The combined material was washed with Et2O (400 mL), and dried on the sintered glass funnel under a stream of N2, with suction, for 16 h to afford 5-amino-6-methylisoquinolin-1(2H)-one (22 g, 64% yield) as a tan crystalline solid. MS (M+H)+ 175.

1. customwas purged with N2
2. additionThe suspension was treated with 10% Pd/C (10 g)
3. customthe reaction vessel was purged with H2
4. customconsumed, approximately 100 h
5. customThe reaction mixture was purged with N2
6. filtrationfiltered through a pad of Celite
7. washThe pad was washed with MeOH (400 mL)
8. additionthe combined filtrate was treated with water (80 mL)
9. concentrationconcentrated in vacuo to ˜200 mL
10. additionThe dark mixture was diluted with 200 mL MeOH
11. additionadded in a thin stream to ice water (1.5 L)
12. stirringstirred in a large beaker
13. filtrationThe resulting fine precipitate was collected by suction filtration
14. customsatd NaHCO3 (100 mL) and sonicated for 1 min
15. filtrationThe solid was collected by suction filtration
16. washwashed with water (2×100 mL), Et2O (100 mL)
17. customair-dried overnight
18. customto afford 28 g as a grey powder
19. additiontreated with decolorizing carbon (˜10 g)
20. filtrationThe hot suspension was filtered through Celite
21. washThe filter cake was washed with MeOH (200 mL)
22. concentrationthe filtrate was concentrated in vacuo to ˜200 mL
23. additionThe dark brown solution was added to water (1.2 L)
24. customto afford a fine crystalline precipitate
25. filtrationThe solid was collected by suction filtration on a medium-sintered glass frit
26. washwashed with water (500 mL)
27. customA second crop precipitated in the filtrate
28. filtrationwas collected by suction filtration
29. washwashed with water (100 mL)
30. additionadded to the first crop
31. washThe combined material was washed with Et2O (400 mL)
32. dry with materialdried on the sintered glass funnel under a stream of N2, with suction, for 16 h

ORD record

ord-464b81c6d0e649fe8c679d812d3a1589

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989461B2