合成路线1

The condensation of 2-(3-pyridinyl)tetrahydrothiopyran-2-carboxylic acid (I) with L-proline tert-butyl ester (II) by means of SOCl2 gives the corresponding amide as a diastereomeric mixture (S,S)-(III) + (R,S)-(III) that is separated by chromatography. The desired isomer (R,S)-(III) is hydrolyzed with conc. HCl to yield 2-(3-pyridinyl)tetrahydrothiopyran-2-carboxylic acid (R)-(IV), which is treated first with SOCl2 and methylamine, and then with Lawesson reagent or P2S5 to afford the thioamide (R)-(V). The reaction of (R)-(V) with methyl iodide, n-BuLi and H2S in pyridine provides the dithioester (R)-(VI), which is carefully oxidized with MCPBA in dichloromethane to provide the corresponding sulfoxide as a diastereomeric mixture (1R,2R)-(VII) + (1S,2R)-(VII) that is separated by chromatography. Finally, the desired isomer (1R,2R)-(VII) is treated with methylamine in ethanol to furnish the target thioamide.