Small molecule inhibitors of rotamase enzyme activity

A method of making a pyrrolidinyl alkyl oxamate, comprising the steps of:

• i) reacting L-proline methyl ester hydrochloride with methyl oxalyl chloride to form methyl (2S)-1-(1,2-dioxo-2-methoxyethyl)-2-pyrrolidinecarboxylate;
• ii) reacting methyl (2S)-1-(1,2-dioxo-2-methoxyethyl)-2-pyrrolidinecarboxylate with a carbon nucleophile of the form R-Li or R-MgX, wherein:
• X is a halogen;
• and
• R is selected from the group consisting of a C1-C9 straight or branched chain alkyl or alkenyl group optionally substituted with C3-C8 cycloalkyl, C3 or C5 cycloalkyl, C5-C7 cycloalkenyl, Ar1, where said alkyl, alkenyl, cycloalkyl or cycloalkenyl groups may be optionally substituted with C1-C4 alkyl, C1-C4 alkenyl, or hydroxy, where Ar1 is selected from the group consisting of 1-naphthyl, 2-naphthyl, 2-indolyl, 3-indolyl, 2-furyl, 3-furyl, 2-thiazolyl, 2-thienyl, 3-thienyl, 2-, 3-, 4-pyridyl, and phenyl, having one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, C1-C6 straight or branched alkyl or alkenyl, C1-C4 alkoxy or C1-C4 alkenyloxy, phenoxy, benzyloxy, and amino.