Histamine Antagonists. Basically Substituted Pyridine Derivatives

Atom economical coupling of benzophenone and N-heterocyclic aromatics with SmI2

“…The OCCN torsion angle is small two very different sets of Sm-N distances are noted. The reactivity clearly resembles the preparation of carbinols from pyridine and ketones but without the use of mercuric chloride 17 or any coupling additives other than SmI 2 , a much cleaner and atom economical pathway, as reported by Helquist. 18,19 However, the useful reaction was not reported with neat pyridine and although this reactivity does not happen at room temperature with neat pyridine, a solution of II was heated at 110 °C for 16 h and turned yellow.…”

“…15 One important aspect of this peculiar chemistry lies in the preparation of a-substituted pyridinemethanols (carbinols) from pyridine and various ketones (Scheme 1), 16 which originally employed either aluminium or magnesium in combination with mercuric chloride and iodine or a mixture of Hg/HgCl. 17 Greener alternatives for carbinol syntheses are reported from aldehydes using strong Lewis acids but prevent the synthesis of tertiary alcohols. 16 Scheme 1.…”

Minisci reactions: Versatile CH-functionalizations for medicinal chemists

“…118,119 An example from 1948 details the use of an Emmert reaction to prepare substituted pyridines as histamine antagonists. 120 A key intermediate 61 was prepared from pyridine and benzaldehyde in 39% yield. Intermediate 61 could be elaborated to the desired target histamine antagonist 62 (Scheme 41).…”

“…Scheme 40 Synthesis of the analgesic licofelone (ML3000) and a13 C-labelled bilin 113,116. Scheme 41 Use of Emmert reactions to provide histamine antagonists and potassium channel openers 120,121. …”

The Acylation and Alkylation of Imidazolines and Some New Types of Imidazolines1

“…137-139°and was identical with the product obtained formerly by other methods. 2 2-Acetoxy-l,3-diacetyl-2-phenylimidazolidine (IX).-2-Phenylimidazoline (14.62 g., 0.1 mole)7 was dissolved in 50 ml. of dry pyridine and 75 ml.…”