Thionyl Chloride → HCID 86664573, compound

To a suspension of (R)-5-(2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation E, 50.0 mg, 0.153 mmol) in CCl4 (1.5 mL) was added thionyl chloride (182 mg, 1.53 mmol) and mixture heated at reflux for 4 hours (homogeneous). The mixture was cooled to ambient temperature and was concentrated to a brittle beige foam. DMAP (3.7 mg, 0.031 mmol), methylhydroxylamine HCl (38.4 mg, 0.460 mmol) and dry THF (2 mL) were added and mixed. Diisopropylethylamine (79.2 mg, 0.613 mmol) was added, and the reaction flushed with N2 and stirred at ambient temperature for 18 hours. The mixture was diluted with H2O (4 mL) and extracted with EtOAc and the combined extracts were washed with 1M Na2CO3, H2O and saturated NaCl. The solution was dried over MgSO4/activated carbon and filtered through a SiO2 plug eluting with EtOAc. The mixture was concentrated to give a white foam that was dissolved in minimal CH2Cl2 and treated with dry hexanes to give a fine white suspension. The mixture was concentrated to give the title compound as white solid (42 mg, 77%). MS (apci) m/z=356.0 (M+H).

1. temperatureheated
2. temperatureat reflux for 4 hours (homogeneous)
3. concentrationwas concentrated to a brittle beige foam
4. additionmixed
5. customthe reaction flushed with N2
6. additionThe mixture was diluted with H2O (4 mL)
7. extractionextracted with EtOAc
8. washthe combined extracts were washed with 1M Na2CO3, H2O and saturated NaCl
9. dry with materialThe solution was dried over MgSO4/activated carbon
10. filtrationfiltered through a SiO2 plug
11. washeluting with EtOAc
12. concentrationThe mixture was concentrated
13. customto give a white foam that
14. customto give a fine white suspension
15. concentrationThe mixture was concentrated

ORD record

ord-a3e969e56fbe40fd8736fb1e4c264eb0

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791123B2