Azetidine → 5-(Azetidin-1-ylmethyl)-1-methyl-3-nitro-1H-pyrazole

To a solution of 5-(bromomethyl)-1-methyl-3-nitro-1H-pyrazole (436 mg, 1.98 mmol) in tetrahydrofuran (10 mL) was added azetidine (141 mg, 0.17 mL, 2.48 mmol) and diisopropylethyl amine (307 mg, 0.42 mL, 2.38 mmol) drop wise and the resulting mixture was stirred at room temperature for 24 h. The solution was concentrated and the residue dissolved in dichloromethane (50 mL), washed with water (50 mL). The aqueous layer was extracted with methylene chloride (2×50 mL) and the organic phases combined and dried over magnesium sulfate. The resulting mixture was filtered and evaporated and the residue purified by flash chromatography (40 g, 1% to 5% methanol in dichloromethane) to give 5-(azetidin-1-ylmethyl)-1-methyl-3-nitro-1H-pyrazole (349 mg, 90%) as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.97 (quin, J=6.99 Hz, 2 H) 3.15 (t, J=6.99 Hz, 4 H) 3.59 (s, 2 H) 3.88 (s, 3 H) 6.89 (s, 1 H).

1. concentrationThe solution was concentrated
2. dissolutionthe residue dissolved in dichloromethane (50 mL)
3. washwashed with water (50 mL)
4. extractionThe aqueous layer was extracted with methylene chloride (2×50 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationThe resulting mixture was filtered
7. customevaporated
8. customthe residue purified by flash chromatography (40 g, 1% to 5% methanol in dichloromethane)

ORD record

ord-8e96c09aec17431a85baf5dbeea43b6a

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889682B2