Diisopropylethylamine → 1H-Pyrazole, 5-[(3,3-difluoro-1-azetidinyl)methyl]-1-methyl-3-nitro-

Temperature

65 °C

A sealed tube with a magnetic stirrer was charged with DMF (5 mL), 5-(Bromomethyl)-1-methyl-3-nitro-1H-pyrazole 156d (0.39 g, 1.78 mmol), 3,3-difluoroazetidine hydrochloride (276 mg, 2.13 mmol) and DIPEA (0.8 mL, 4.45 mmol). The reaction mixture was heated at 65° C. for 3-5 h. After this time the reaction was concentrated to dryness under reduced pressure, and the resulting residue was diluted with a mixture of Ethyl Acetate (15 mL) and water (15 mL). The aqueous layer was separated and extracted with Ethyl Acetate (2×15 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure to afford a quantitative yield of 156e as yellow oil, which was used without further purification for the next step. MS (ESI+) m/z 233.0 (M+H).

1. concentrationAfter this time the reaction was concentrated to dryness under reduced pressure
2. additionthe resulting residue was diluted with a mixture of Ethyl Acetate (15 mL) and water (15 mL)
3. customThe aqueous layer was separated
4. extractionextracted with Ethyl Acetate (2×15 mL)
5. dry with materialThe combined organic extracts were dried over sodium sulfate
6. concentrationconcentrated under reduced pressure

ORD record

ord-e18b4a3b71074817afcaec5ef5a08628

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618107B2