New building blocks for fluorinated imidazole derivatives: preparation of beta-fluoro- and beta,beta-difluorohistamine.
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.
Dolensky
B
B
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kirk
K L
KL
D005461:Fluorine / Q000737:chemistry*; D006632:Histamine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry
D006845:Hydrocarbons, Fluorinated; C431473:difluorohistamine; C431474:fluorohistamine; D005461:Fluorine; D006632:Histamine