Pyrazole → 2-methyl-4-(1H-pyrazol-1-yl)pyridine

HRID 41595

Reaction equation

Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.[NH:9]1[CH:13]=[CH:12][CH:11]=[N:10]1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[CH3:8][C:4]1[CH:3]=[C:2]([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:7]=[CH:6][N:5]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a mixture of 4-bromo-2-methylpyridine [22282-99-1] (350 mg, 2.05 mmol), 1H-pyrazole (140 mg, 2.05 mmol), 1,10-phenanthroline (74 mg, 0.41 mmol) and K2CO3 (567 mg, 4.1 mmol) in toluene (2 mL), CuI (19 mg, 0.1 mmol) was added and the reaction mixture was heated at 120° C. for 70 h in a sealed tube. The reaction mixture was cooled to rt, quenched with water (50 mL) and extracted with dichloromethane (150 mL). The organic layer was washed with brine and dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified flash column chromatography (eluent: 30% ethyl acetate in hexane) to yield the title compound (300 mg, 92%). [1H NMR (300 MHz, CDCl3) ♀ ppm 8.53 (d, 1H), 8.02 (d, 1H), 7.77 (d, 1H), 7.55 (d, 1H), 7.44-7.40 (m, 1H), 6.52 (t, 1H), 2.62 (s, 3H); TLC Rf=0.28 (ethyl acetate/hexane 30:70)].

Workup

additionwas added
temperatureThe reaction mixture was cooled to rt
customquenched with water (50 mL)
extractionextracted with dichloromethane (150 mL)
washThe organic layer was washed with brine
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude product was purified flash column chromatography (eluent: 30% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-ba31f049f5f24f55a3d18e92a376ae81
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530648B2

Linked notes

Loading…