1,1,3,3-Tetramethylguanidine → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(2-ethyl-4-methylthiazole-5-yl)propenoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

1,1,3,3-Tetramethylguanidine (107 mg, 0.9 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 141; 300 mg, 0.6 mmol) in dichloromethane (10 mL) at ˜5° C. The solution was stirred at ˜5° C. for 30 min and then 2-ethyl-4-methylthiazole-5-carboxaldehyde (Example 60; 192 mg, 1.2 mmol) was added. The solution was stirred overnight at room temperature, then silica gel was added and the solvent was evaporated. The residue was applied to a column of silica gel and unreacted 2-ethyl-4-methylthiazole-5-carboxaldehyde was eluted with 50% ethyl acetate/hexanes. Evaporation of the appropriate fractions eluted with 5% methanol/dichloromethane gave (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(2-ethyl-4-methylthiazole-5-yl)propenoic acid methyl ester (110 mg, 35% yield) as a colorless solid, mp>200° C.

Provenance & Evidence