The condensation of 2-(4-hydroxyphenyl)acetic acid methyl ester (XIII) with 2-(tert-butoxycarbonylamino)ethanol (XV) by means of diethyl azodicarboxylate (DEAD) in THF gives 2-[4-[2-(tert-butoxy carbonyl- amino)ethoxy]phenyl]acetic acid methyl ester (XVI), which is deprotected with TFA in dichloromethane yielding the 2-aminoethoxy derivative (XVII). The addition of (XVII) to the oxiranyl derivative (XVIII) in refluxing methanol affords the intermediate (XIX), which is reduced with SnCl2 in refluxing methanol to give the 6-aminopyridine derivative (XX). Finally, this compound is hydrolyzed to the target compound with KOH in methanol/water. The oxirane intermediate (XVIII) has been obtained by stereocontrolled reductive cyclization of 6-(2-bromoacetyl)tetrazolo[1,5-a]pyridine (XXI) with commercial (R)-Alpine Borane in THF.

The condensation of 2-(4-hydroxyphenyl)acetic acid methyl ester (XIII) with 2-(tert-butoxycarbonylamino)ethanol (XV) by means of diethyl azodicarboxylate (DEAD) in THF gives 2-[4-[2-(tert-butoxy carbonyl- amino)ethoxy]phenyl]acetic acid methyl ester (XVI), which is deprotected with TFA in dichloromethane yielding the 2-aminoethoxy derivative (XVII). The addition of (XVII) to the oxiranyl derivative (XVIII) in refluxing methanol affords the intermediate (XIX), which is reduced with SnCl2 in refluxing methanol to give the 6-aminopyridine derivative (XX). Finally, this compound is hydrolyzed to the target compound with KOH in methanol/water. The oxirane intermediate (XVIII) has been obtained by stereocontrolled reductive cyclization of 6-(2-bromoacetyl)tetrazolo[1,5-a]pyridine (XXI) with commercial (R)-Alpine Borane in THF.

The acetylation of 5-bromopyridine-2-amine (I) with acetic anhydride in AcOH gives the expected amide (II), which is alkylated with ethylene by means of palladium acetate, tri p-tolylphosphine and triethylamine in hot acetonitrile to yield N-(5-vinylpyridin-2-yl)acetamide (III). The regioselective dihydroxylation of the vinyl group of (III) with AD-Mix-B in tert-butanol affords N-[5-(1(R),2-dihydroxyethyl)pyridin-2-yl]acetamide (IV), which is monotosylated with Ts-Cl in cool pyridine to give the tosylate (V). The reaction of (V) with potassium tert.-butoxide in THF yields the epoxide (VI), which is condensed with 2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide (VII) in hot toluene/DMSO to provide the expected addition product (VIII). Finally, this compound is treated with 6N HCl on a steam bath. The intermediate 2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide (VII) has been obtained as follows: The reaction of benzyl chloroformate (IX) with ethanolamine (X) by means of NaHCO3 in water gives the carbamate (XI), which is condensed with 2-(4-hydroxyphenyl)-N-methylacetamide (XII) (obtained by reaction of the corresponding methyl ester (XIII) with methylamine), by means of PPh3 and diisopropyl azodicarboxylate (DIAD) in THF yielding the intermediate (XIV). Finally, this compound is submitted to elimination of the carbamate protecting group by hydrogenation with H2 over Pd/C in methanol to provide the target intermediate (VII).

The acetylation of 5-bromopyridine-2-amine (I) with acetic anhydride in AcOH gives the expected amide (II), which is alkylated with ethylene by means of palladium acetate, tri p-tolylphosphine and triethylamine in hot acetonitrile to yield N-(5-vinylpyridin-2-yl)acetamide (III). The regioselective dihydroxylation of the vinyl group of (III) with AD-Mix-B in tert-butanol affords N-[5-(1(R),2-dihydroxyethyl)pyridin-2-yl]acetamide (IV), which is monotosylated with Ts-Cl in cool pyridine to give the tosylate (V). The reaction of (V) with potassium tert.-butoxide in THF yields the epoxide (VI), which is condensed with 2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide (VII) in hot toluene/DMSO to provide the expected addition product (VIII). Finally, this compound is treated with 6N HCl on a steam bath. The intermediate 2-[4-(2-aminoethoxy)phenyl]-N-methylacetamide (VII) has been obtained as follows: The reaction of benzyl chloroformate (IX) with ethanolamine (X) by means of NaHCO3 in water gives the carbamate (XI), which is condensed with 2-(4-hydroxyphenyl)-N-methylacetamide (XII) (obtained by reaction of the corresponding methyl ester (XIII) with methylamine), by means of PPh3 and diisopropyl azodicarboxylate (DIAD) in THF yielding the intermediate (XIV). Finally, this compound is submitted to elimination of the carbamate protecting group by hydrogenation with H2 over Pd/C in methanol to provide the target intermediate (VII).