Ammonium Chloride → HCID 11950324, compound

Temperature

-78 °C

A solution of di(tert-butyl) 1-methyl-2-propyl-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate (1.32 g, 3.00 mmol) in anhydrous tetrahydrofuran (THF) (30 mL) was cooled to −78° C. under an argon atmosphere. tert-Butyllithium (4.4 mL of a 1.7 M solution in pentane) was added over a period of five minutes, and the resulting dark-colored solution was stirred at −78° C. for 30 minutes. Tetrahydro-4H-pyran-4-one (901 mg, 9.0 mmol) was added, and reaction mixture was stirred for 10 minutes. The −78° C. bath was replaced with a 0° C. bath, and then saturated aqueous ammonium chloride (30 mL) was added. The aqueous layer was separated and extracted three times with tert-butyl methyl ether, and the combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (1.3 g) was purified by automated flash chromatography (eluting with ethyl acetate) and heated in refluxing 1 M hydrogen chloride in ethanol (50 mL) for one hour. The solution was allowed to cool to room temperature and then made basic with the addition of 2 M aqueous sodium carbonate. The resulting solution was extracted four times with chloroform, and the combined extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (1.2 g) was purified by automated flash chromatography and recrystallized from acetonitrile to provide 430 mg of 4-[(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)methyl]tetrahydro-2H-pyran-4-ol as a white solid, mp 209-211° C.

1. customreaction mixture
2. stirringwas stirred for 10 minutes
3. customThe −78° C. bath
4. customwas replaced with a 0° C.
5. customThe aqueous layer was separated
6. extractionextracted three times with tert-butyl methyl ether
7. dry with materialthe combined organic fractions were dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue (1.3 g) was purified by automated flash chromatography (eluting with ethyl acetate)
11. temperatureheated
12. temperaturein refluxing 1 M hydrogen chloride in ethanol (50 mL) for one hour
13. temperatureto cool to room temperature
14. additionmade basic with the addition of 2 M aqueous sodium carbonate
15. extractionThe resulting solution was extracted four times with chloroform
16. dry with materialthe combined extracts were dried over magnesium sulfate
17. filtrationfiltered
18. concentrationconcentrated under reduced pressure
19. customThe residue (1.2 g) was purified by automated flash chromatography
20. customrecrystallized from acetonitrile

ORD record

ord-b116d843c00245c687bd3b98d794295a

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07943636B2