Reaction SMILES: Cl[C:2]1[C:7]([NH:8][C:9](=[O:15])[CH2:10][O:11]C(=O)C)=[C:6](Cl)[CH:5]=[C:4]([CH3:17])[N:3]=1.C1OCCOCCOCCOCCOCCOC1.O.[CH3:37][S-:38].[Na+].C[S:41]([CH3:43])=O>C(Cl)(Cl)Cl>[CH3:37][S:38][C:2]1[C:7]([NH:8][C:9](=[O:15])[CH2:10][OH:11])=[C:6]([S:41][CH3:43])[CH:5]=[C:4]([CH3:17])[N:3]=1
Reactant: CC(=O)OCC(=O)Nc1c(Cl)cc(C)nc1Cl
Reactant: CS(C)=O
Reactant: C[S-]
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: CSc1cc(C)nc(SC)c1NC(=O)CO
Temperature: 52.5 °C
Reaction time: 2.5 h
Yield: 54.4 %

Procedure:
Sodium thiomethoxide powder (5.06 g, 72.19 mmol) was added to a solution of N-[2,4-dichloro-6-methylpyridin-3-yl]-2-acetyloxyacetamide (5.00 g, 18.04 mmol) and 18-crown-6 (0.48 g, 1.82 mmol) in dimethyl sulfoxide (40 mL), followed by stirring at an internal temperature of 75 to 81° C. for 1 hour. After the reaction mixture was left to cool, chloroform and water were added thereto. The formed organic layer was separated, and the aqueous layer was extracted with chloroform. The obtained organic layers were combined, followed by washing sequentially with water and saturated brine. The thus-washed organic layer was dried over sodium sulfate anhydrate, and the solvent was removed under reduced pressure. The aqueous layer obtained in the above washing was extracted with chloroform, and the organic layer was washed sequentially with water and saturated brine. The thus-washed organic layer was dried over sodium sulfate anhydrate, and the solvent was removed. The residues were combined, followed by purification through silica gel column chromatography (hexane/acetone=5/2), to thereby yield N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]-2-hydroxyacetamide as a colorless solid (4.06 g, yield: 87.1%). The solid was recrystallized from ethyl acetate, to thereby yield colorless needles. (B) N-[2,4-Dichloro-6-methylpyridin-3-yl]-2-acetyloxyacetamide (135.0 g, 487 mmol) and 18-crown-6 (12.9 g, 48.8 mmol) were dissolved in dimethyl sulfoxide (1,350 mL). Under cooling with water, sodium thiomethoxide (powder) (170.7 g, 2,435 mmol) was added thereto. The reaction mixture was heated, followed by stirring at an internal temperature of 50 to 55° C. for 2.5 hours. After the reaction mixture was water-cooled, water (1,350 mL) and chloroform (1,350 mL) were added thereto. The formed organic layer was collected, and the aqueous layer was extracted with chloroform (675 mL). The obtained organic layers were combined, followed by washing with saturated brine (2,025 mL). The thus-washed organic layer was dried over sodium sulfate anhydrate, and the solvent was removed under reduced pressure. Subsequently, methanol (135 mL) and water (1,350 mL) were added to the residue, and the resultant mixture was stirred at an internal temperature of 23 to 25° C. for 1.5 hours. The crystals that precipitated were collected through filtration, followed by washing with water and drying at room temperature, to thereby the crude target product. The crude product was dissolved in chloroform (380 mL) through heating, and the reaction mixture was cooled. The cooled mixture was stirred at an internal temperature of 5° C. or lower for 2 hours. The crystals that precipitated were collected through filtration, followed by washing with cooled chloroform (76 mL) and drying at room temperature, to thereby yield N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]-2-hydroxyacetamide (68.49 g, yield: 54.4%, HPLC: 97.47%).