New building blocks for fluorinated imidazole derivatives: preparation of beta-fluoro- and beta,beta-difluorohistamine. |
| |
| Authors: | B Dolensky K L Kirk |
| |
| Affiliation: | Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. |
| |
| Abstract: | We demonstrate that "FBr" addition to 1-trityl-4-vinyl-1H-imidazole (7) provides a convenient route to side-chain-fluorinated histamines. Thus, addition of "FBr" to the double bond of 7 occurs with Markovnikov regioselectivity to produce 4-(2-bromo-1-fluoroethyl)-1-trityl-1H-imidazole (8). Substitution with azide, reduction, and removal of the trityl group provide beta-fluorohistamine (1) as the dihydrochloride. Elimination of HBr from 8 followed by a second addition of "FBr" gives 4-(2-bromo-1,1-difluoroethyl)-1-trityl-1H-imidazole (15). This was similarly converted to beta,beta-difluorohistamine (2) as the dihydrochloride. |
| |
| Keywords: | |
|
|
