Glyoxal → tert-Butyl 7H-pyrrolo[3',4':3,4]pyrazolo[1,5-b][1,2,4]triazine-8(9H)-carboxylate

To a stirred solution of 0.2 g (0.89 mmol) of tert-butyl 3-amino-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate in N,N-dimethylformamide (4 mL) at −10° C. was added 0.37 g (5.6 mmol) of powdered potassium hydroxide. The reaction mixture was stirred between 0° C. and −10° C. for 20 min. To this mixture was added 0.2 g (1.78 mmol) of hydroxylamine-O-sulfonic acid in eight portions over 20 min while maintaining the temperature between 0° C. and −10° C. Stirring was continued for 45 min while keeping the temperature below 5° C. Ethanol (4 mL) was added slowly to maintain the temperature below 5° C. and 0.2 mL (1.78 mmol) of 40% glyoxal in water was added. The reaction mixture was stirred below 5° C. for 15 min, warmed to ambient temperature over 15 min and stirred at ambient temperature for 45 min. The reaction mixture was cooled to below 5° C. and a 1:1 mixture of half saturated aqueous ammonium chloride/brine (15 mL) was added. The reaction mixture was extracted with ethyl acetate (4×15 mL), and the combined organic phases washed with saturated aqueous brine (15 mL), dried over anhydrous magnesium sulfate, filtered and the solvent evaporated in vacuo. The residue was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 40% hexanes/ethyl acetate gradient) to yield the title compound as a yellow solid. LC/MS 262.2 (M+1).

1. temperaturewhile maintaining the temperature between 0° C. and −10° C
2. stirringStirring
3. waitwas continued for 45 min
4. customthe temperature below 5° C
5. additionwas added
6. stirringThe reaction mixture was stirred below 5° C. for 15 min
7. stirringstirred at ambient temperature for 45 min
8. temperatureThe reaction mixture was cooled to below 5° C.
9. additionwas added
10. extractionThe reaction mixture was extracted with ethyl acetate (4×15 mL)
11. washthe combined organic phases washed with saturated aqueous brine (15 mL)
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationfiltered
14. customthe solvent evaporated in vacuo
15. customThe residue was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 40% hexanes/ethyl acetate gradient)

ORD-Eintrag

ord-1ba9dd0d47674106b9b9da396928b0d6

Quelldatensatz

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07855206B2