Potassium Carbonate → HCID 86669252, compound

Temperature

90 °C

1-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (for a preparation see Example 61) (100 mg, 0.271 mmol) was dissolved in ethanol (1 mL) and Toluene (1 mL), mixed with potassium carbonate (74.9 mg, 0.542 mmol), 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (96 mg, 0.325 mmol, available from Aldrich) and tetrakis(triphenylphosphine)palladium(0) (15.65 mg, 0.014 mmol) and refluxed under nitrogen at 90° C. for 22 hours reaction time. The reaction was left to stand at room temperature for 2.5 days. It was refluxed again at 90° C. for 24 hours. A second sample of 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (96 mg, 0.325 mmol) was added to the reaction mixture after this time and heating continued. A third sample of 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (96 mg, 0.325 mmol) was added to the reaction mixture after 102.5 hours reaction time and the mixture was allowed to stir overnight under nitrogen at the same temperature. Another sample of 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (96 mg, 0.325 mmol) was added after 199 hours total reaction time. After 248 hours reaction time the mixture was cooled to room temperature and partitioned between distilled water (40 mL) and EtOAc (40 mL). The organic and aqueous layers were run off and the latter was extracted 3 more times using EtOAc (3×40 mL). Organic fractions were combined, washed (brine (50 mL), dried (sodium sulfate), filtered and evaporated to dryness to give an orange/brown oil (248 mg). The residue was purified by SP4 on a 25+S silica cartridge using a gradient of 0 to 2.5% 2M methanloic ammonia in ethyl acetate. Product-containing fractions were evaporated to dryness and purified again using MDAP. Product-containing fractions were evaporated to dryness to give a clear, colourless solid (18 mg). LCMS (Method C): Rt=0.73, MH+=357

1. customreaction time
2. waitThe reaction was left
3. temperatureIt was refluxed again at 90° C. for 24 hours
4. temperatureheating
5. customreaction time
6. customAfter 248 hours reaction time the mixture
7. temperaturewas cooled to room temperature
8. custompartitioned
9. distillationbetween distilled water (40 mL) and EtOAc (40 mL)
10. extractionthe latter was extracted 3 more times
11. washwashed (brine (50 mL)
12. dry with materialdried (sodium sulfate)
13. filtrationfiltered
14. customevaporated to dryness

ORD record

ord-4a8cac2bcfb74fbaab1d8740db813ed1

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697725B2