Preparation of nitriles of fused ring pyridine derivatives
AssigneeJohn Wyeth & Brother Limited
InventorRobin G. Shepherd
Life of this patent
Estimating the term…
Abstract
Nitriles of fused ring pyridine compounds such as 5,6,7,8-tetrahydroquinolines are prepared from metal derivatives of the starting compounds such as 8-litho-5,6,7,8-tetrahydroquinolines which have been prepared by treating a 5,6,7,8-tetrahydroquinoline with a metal amide prepared in situ from a metal alkyl and an N-benzylidine-N-alkylamine.
Claims7
A method of preparing nitriles of formula I ##STR6## or acid addition salts thereof, wherein R.sup.11, R.sup.12, R.sup.13, R.sup.14 and R.sup.15 are the same or different and represent hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 4-6 carbon atoms, phenylalkyl of 7-12 carbon atoms or phenyl groups any of which groups may be mono or disubstituted by alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, fluorine or trifluoromethyl or R.sup.11 and R.sup.12 taken together, or R.sup.12 and R.sup.13 taken together, form a 5,6 or 7 membered saturated carbocyclic ring, R.sup.14 and R.sup.15 may also represent alkoxy of 1-6 carbon atoms, n is 1, 2 or 3, in which a compound of formula II ##STR7## where R.sup.1 is hydrogen, phenyl, phenyl substituted by alkyl of 1-6 carbon atoms, or a tertiary alkyl group of 4 to 6 carbon atoms;
- R.sup.2 is phenyl, phenyl substituted by alkyl of 1-6 carbon atoms or a tertiary alkyl group of 4-6 carbon atoms;
- R.sup.3 is a branched chain alkyl of 3 to 6 carbon atoms;
- is reacted with a metal alkyl MR where R is an alkyl group of 2-6 carbon atoms, a phenyl or phenyl substituted by alkyl of 1-6 carbon atoms and M is lithium, sodium or potassium, in an inert non-polar solvent to obtain a compound of formula III ##STR8## wherein R, R.sup.1, R.sup.2, R.sup.3 and M are as defined above, and this compound is treated with a compound of formula IV ##STR9## where R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15 and n are as defined in connection with formula I to obtain a compound of formula V ##STR10## where M, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15 and n are as defined above and the compound of formula V is treated with a compound of formula RaRbNCN wherein Ra and Rb are the same or different and represent alkyl of 1-6 carbon atoms, cycloalkyl of 4-6 carbon atoms or phenylalkyl of 7-12 carbon atoms, or Ra and Rb may be joined to form a 5,6 or 7 membered saturated heterocyclic ring with the nitrogen atom to which they are attached and the product is treated with a proton source selected from water, an aqueous inorganic acid, an alkanol having 1-6 carbon atoms, an alkanoic acid having 1-6 carbon atoms or ammonium chloride to obtain the nitrile of formula I.
Dependencies are inferred from the claim text.