Phosphorus oxychloride → Ethyl 4-chloro-1-ethyl-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

Temperature

150 °C

A mixture of 5-amino-1-ethylpyrazole (1.614 g, 14.5 mmol) and diethyl 2-(1-ethoxyethylidene)malonate (3.68 g, 16.0 mmol, as described by P. P. T. Sah, J. Amer. Chem. Soc., 1931, 5, 1836) was heated at 150° C. under Dean Stark conditions for 5 hours. Phosphorous oxychloride (25 ml) was carefully added to the mixture and the resulting solution was heated at 130° C. under reflux for 18 hours. The mixture was concentrated in vacuo, then the residual oil was carefully added, with cooling, to water (100 ml). The resulting mixture was extracted with DCM (3×100 ml) and the combined organic extracts were dried over anhydrous sodium sulphate and concentrated in vacuo. The residual oil was purified by Biotage chromatography (silica, 90 g) eluting with ethyl acetate-petrol (1:19). Fractions containing the desired product were combined and concentrated in vacuo to afford Intermediate 58 (1.15 g). LCMS showed MH+=268; TRET=3.18 min.

1. temperaturethe resulting solution was heated at 130° C.
2. temperatureunder reflux for 18 hours
3. concentrationThe mixture was concentrated in vacuo
4. additionthe residual oil was carefully added
5. temperaturewith cooling, to water (100 ml)
6. extractionThe resulting mixture was extracted with DCM (3×100 ml)
7. dry with materialthe combined organic extracts were dried over anhydrous sodium sulphate
8. concentrationconcentrated in vacuo
9. customThe residual oil was purified by Biotage chromatography (silica, 90 g)
10. washeluting with ethyl acetate-petrol (1:19)
11. additionFractions containing the desired product
12. concentrationconcentrated in vacuo

ORD record

ord-afca39a312e94c67aaabacf8e23b9edc

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07528148B2