Thionyl Chloride → HCID 178489932, compound

Activation of 0.46 g (2.23 mmol) of 2-cyclopropylmethanesulfonyl-2-methyl-propionic acid as the corresponding acid chloride is achieved by treatment with thionyl chloride (5 mL, 69 mmol) at 70° C. for 2 h. The reaction is cooled to room temperature and excess thionyl chloride is removed under reduced pressure. The crude acid chloride is dissolved in THF (5 mL) and N,N-diisopropylethylamine (0.54 mL, 5.64 mmol) is added followed by 0.3 g (2.6 mmol) of 5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylamine. After complete addition the reaction is heated to 70° C. for 36 h. The reaction is cooled to room temperature and the solvent is removed under reduced pressure. The residue is dissolved in DCM (20 mL) and washed with saturated aqueous NaHCO3 solution (20 mL). The aqueous layer is back-extracted with DCM (2×20 mL). The combined organic layers are dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure. The residue is slurried in DCM/ether (1/1, 10 mL) to yield 0.398 g of 2-cyclopropylmethanesulfonyl-N-[5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-2-methyl-propionamide. Yield: 46%; ES-MS: m/z 379 [M+H]

1. customexcess thionyl chloride is removed under reduced pressure
2. dissolutionThe crude acid chloride is dissolved in THF (5 mL)
3. additionAfter complete addition the reaction
4. temperatureis heated to 70° C. for 36 h
5. temperatureThe reaction is cooled to room temperature
6. customthe solvent is removed under reduced pressure
7. dissolutionThe residue is dissolved in DCM (20 mL)
8. washwashed with saturated aqueous NaHCO3 solution (20 mL)
9. extractionThe aqueous layer is back-extracted with DCM (2×20 mL)
10. dry with materialThe combined organic layers are dried over Na2SO4
11. filtrationfiltered
12. concentrationthe filtrate is concentrated under reduced pressure

ORD record

ord-7044b7296a06435ca67f29a372b16bd8

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08048899B2