Benzenesulfonyl chloride → methyl [4-amino-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl]carbamate

Temperature

50 °C

A suspension of methyl [1-(2-methylpropyl)-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl]carbamate (0.9 g, 3 mmol) in methanol (25 mL) was stirred vigorously and heated to 50° C. Concentrated ammonium hydroxide (0.95 mL, 14 mmol) was added followed by benzenesulfonyl chloride (1.06 g, 5.99 mmol), which was added dropwise. The mixture was stirred for two hours at 50° C. An analysis by LC/MS indicated the reaction was incomplete. Additional benzenesulfonyl chloride (1.06 g) and concentrated ammonium hydroxide (0.95 mL) were added, and the reaction mixture was stirred overnight at 45° C. The solvent was removed under reduced pressure, and the residue dissolved in chloroform (100 mL). The solution was washed sequentially with aqueous sodium carbonate (2×100 mL of 4% w/w) and water (100 mL) and then purified by automated flash chromatography (40+M silica cartridge, eluting with 5% to 25% CMA in chloroform) followed by recrystallization from ethyl acetate to provide 0.28 g of methyl [4-amino-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl]carbamate as a yellow solid.

1. additionwas added dropwise
2. stirringThe mixture was stirred for two hours at 50° C
3. stirringthe reaction mixture was stirred overnight at 45° C
4. customThe solvent was removed under reduced pressure
5. dissolutionthe residue dissolved in chloroform (100 mL)
6. washThe solution was washed sequentially with aqueous sodium carbonate (2×100 mL of 4% w/w) and water (100 mL)
7. custompurified by automated flash chromatography (40+M silica cartridge, eluting with 5% to 25% CMA in chloroform)
8. customfollowed by recrystallization from ethyl acetate

ORD record

ord-7738b4cebf0240b0985842622562f2d9

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143270B2