Methane → HCID 86734634, compound

Temperature

25 °C

A 3.16N solution (6.7 cc.) of sodium methoxide in methanol is added to a suspension of 1-methylpiperazine-1-oxide dihydrochloride (2.0 g.) in anhydrous methanol (10 cc.). After stirring for 10 minutes at 25° C., the suspension is treated with decolourising charcoal (0.1 g.) and then filtered. The methanolic filtrate is evaporated under reduced pressure (20 mm.Hg) at 40° C. maximum. The oily residue (2.0 g.) is dissolved in anhydrous acetonitrile (50 cc.) and 2-(7-chloro-1,8-naphthyridin-2-yl)-3-phenoxycarbonyloxy-isoindolin-1-one (2.15 g.) is added. The reaction mixture is heated for 4 hours at 50° C. and then stirred for 48 hours at a temperature of about 25° C., filtered and concentrated under reduced pressure. The residue (3.8 g.) is dissolved in methylene chloride (50 cc.). The solution is passed through a column of Merck silica (0.02 -0.05) (60 g.). Elution is carried out successively with methylene chloride (50 cc.), ethyl acetate (50 cc.), a mixture (50 cc.) of ethyl acetate and methanol (80-20 volume), a mixture (50 cc.) of ethyl acetate and methanol (50--50 by volume), and finally with the same mixture of solvents (100 cc.). This last fraction is evaporated under reduced pressure. The residue obtained (0.9 g., m.p. about 200° C.) is dissolved in acetonitrile (10 cc.) and distilled water (1 cc.), near the boiling point. After cooling to 2° C., the crystals which have appeared are filtered off, washed with ice-cold acetonitrile (0.5 cc.) and dried under reduced pressure (20 mm.Hg). 4-{[2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxo-isoindolin-1-yl]oxycarbonyl{-1-methyl-piperazine-1-oxide dihydrate (0.62 g.), melting at about 200° C. (decomposition), is obtained.

1. filtrationfiltered
2. customThe methanolic filtrate is evaporated under reduced pressure (20 mm.Hg) at 40° C. maximum
3. dissolutionThe oily residue (2.0 g.) is dissolved in anhydrous acetonitrile (50 cc.)
4. addition2-(7-chloro-1,8-naphthyridin-2-yl)-3-phenoxycarbonyloxy-isoindolin-1-one (2.15 g.) is added
5. temperatureThe reaction mixture is heated for 4 hours at 50° C.
6. stirringstirred for 48 hours at a temperature of about 25° C.
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue (3.8 g.) is dissolved in methylene chloride (50 cc.)
10. washElution
11. additiona mixture (50 cc.) of ethyl acetate and methanol (80-20 volume), a mixture (50 cc.) of ethyl acetate and methanol (50--50 by volume), and finally with the same mixture of solvents (100 cc.)
12. customThis last fraction is evaporated under reduced pressure
13. customThe residue obtained (0.9 g., m.p. about 200° C.)
14. distillationdistilled water (1 cc.)
15. temperatureAfter cooling to 2° C.
16. filtrationthe crystals which have appeared are filtered off
17. washwashed with ice-cold acetonitrile (0.5 cc.)
18. customdried under reduced pressure (20 mm.Hg)

ORD record

ord-6a274eaaffc241028c977b1576fe3320

Source dataset

uspto-grants-1977_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04016274