Imidazole → HCID 14885696, compound

To a stirred solution of imidazole (500 mg, 7.35 mmol) and 1,4-dibromobutane (2.6 mL, 22.0) in THF (50 mL) was added 60% NaH (356 mg, 8.81 mmol), and the resultant mixture was refluxed for 2 h and stirred at room temperature overnight. The mixture was quenched with H2O (50 mL) and diluted with CH2Cl2 (75 mL). The aqueous phase was separated and extracted with CH2Cl2 (3×15 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated to dryness. Purification by flash chromatography on silica gel (CH2Cl2/MeOH, 97:3) resulted in partial decomposition of 1-(4-Bromo-butyl)-1H-imidazole. This material was used without any further purification. Using General Procedure A: 3,3″-Dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (94.4 mg, 0.353 mmol), impure 1-(4-Bromo-butyl)-1H-imidazole (145 mg), KI (6.0 mg, 0.035 mmol), DIPEA (0.18 mL, 1.02 mmol), and DMF (3.5 mL) were stirred for 48 h at 60° C. Purification of the crude material by radial chromatography on a 1 mm TLC grade silica gel plate (CH2Cl2/MeOH/NH4OH, 96:2:2) afforded the free base of the title compound (47 mg, 34% over 2 steps) as a colorless oil.

1. customThe mixture was quenched with H2O (50 mL)
2. additiondiluted with CH2Cl2 (75 mL)
3. customThe aqueous phase was separated
4. extractionextracted with CH2Cl2 (3×15 mL)
5. dry with materialThe combined organic extracts were dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. customPurification by flash chromatography on silica gel (CH2Cl2/MeOH, 97:3)

ORD record

ord-1c7c66a5be8a48e784330a04fb0d0483

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07550484B2