Method of synthesizing furo[2,3-b]pyridine carboxylic acid esters

The process for synthesizing a substituted furanyl pyridine of formula II:

• ##STR53## wherein R' is C.sub.1-4 alkyl, or aryl;
• comprising the steps of
• (a) providing one equivalent of the halogenated pyridine of the formula ##STR54## wherein X is Br, I, or Cl;
• (b) reacting the halogenated pyridine of Step (a) with 1.0 or more equivalents of the acetylene ##STR55## in the presence of catalyst selected from one or more of Cu.sup.I, Cu.sup.II, Pd.sup.0, Pd.sup.II, Pt.sup.0, Pt.sup.II, Ni.sup.0, or Ni.sup.II, in 1.0 or more equivalents of base and in ethereal or alcoholic solvent, at a temperature between about 25.degree. C. and about 60.degree. C., for a period of between about 30 minutes and about 48 hours;
• (c) isolating the product ##STR56## (d) reacting the product of Step (c) with in the presence of catalyst selected from Cu.sup.I, Cu.sup.II or Pd.sup.II in ethereal solvent or in alcoholic solvent, at a temperature between about 25.degree. C. and about 75.degree. C. for an incubation time of between about 30 minutes and about 48 hours;
• and
• (e) treating with strong base or halide, at a temperature range of between about 25.degree. C. and about 75.degree. C. for an incubation time of between about 15 minutes and about 24 hours, to give a compound of formula II.

The process for synthesizing the furanyl pyridine ethyl ester of the formula ##STR57## said process comprising the steps of (a) providing one equivalent of the 2-hydroxy pyridine of the formula ##STR58## (b) reacting the pyridine of step (a) with about 1.1 to about 1.5 equivalents of the acetylene ##STR59## in the presence of about 1 mole % Pd.sup.II, about 2 mole % Cu.sup.I, and about 2 mole % PPh.sub.3, in about 2 equivalents of n-BuNH.sub.2 in THF, at a temperature of between about 35.degree. C. and about 39.degree. C., for a period of between about 16 hr and about 27 hr, to give a silylacetylene intermediate;

• (c) reacting the resulting intermediate with about 5 mole % Cu.sup.I in EtOH-Et.sub.3 N (7:3, v/v) at about 70.degree. C. for about 27 hr;
• and
• (d) treating the product of step (c) with K.sub.2 CO.sub.3,
• (e) to give the desired furanyl pyridine ethyl ester.

The process for synthesizing the furanyl pyridine ethyl ester of the formula ##STR60## said process comprising the steps of (a) providing one equivalent of the 2-hydroxy pyridine of the formula ##STR61## (b) reacting the pyridine of step (a) with about 1.1 to about 1.5 equivalents of the acetylene ##STR62## in the presence of about 1 mole % Pd.sup.II, about 2 mole % Cu.sup.I, and about 2 mole % PPh.sub.3, in about 2 equivalents of n-BuNH.sub.2 in THF, at a temperature of between about 35.degree. C. and about 39.degree. C., for a period of between about 16 hr and about 27 hr, to give a silylacetylene intermediate;

• (c) reacting the resulting intermediate with an excess of one equivalent of toluenesulfonic acid in THF at about 60.degree. C. and for about 24 hr;
• and
• (d) treating the product of step (c) with K.sub.2 CO.sub.3,
• (e) to give the desired furanyl pyridine ethyl ester.