Tetrahydrofuran → HCID 178472054, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,6-difluoro-5-iodonicotinic acid (4 g, 14.04 mmol, 1 equiv.) in toluene (30 mL) was added thionyl chloride (5.12 mL, 70.18 mmol, 5 equiv.) followed by DMF (0.5 mL). The reaction was stirred at 110° C. for 1 h. The reaction was concentrated. The residue was re-suspended in THF (15 mL) and added dropwise to a solution of ethyl-3-(dimethylamine)acrylate (2.1 mL, 14.04, 1.1 equiv.) and triethylamine (2.15 mL, 15.44 mmol, 1.1 equiv.) in THF (15 mL). The reaction was stirred at 67° C. for 2 h and cooled to 23° C. (S)-2-amino-3,3-dimethylbutan-1-ol (1.81 g, 15.44 mmol, 1.1 equiv.) was subsequently added and stirred at 23° C. for 30 min. The reaction was quenched with water (40 mL) and ethyl acetate (40 mL). The aqueous layer was extracted with ethyl acetate (2×40 mL), and the organics were dried and concentrated. The compound was purified via silica gel chromatography and concentrated to provide (S)-ethyl 2-(2,6-difluoro-5-iodonicotinoyl)-3-(1-hydroxy-3,3-dimethylbutan-2-ylamino)acrylate Intermediate 80 (4.49 g, 66%). Calcd for C17H21F2IN2O4 [M+H]+: 482.9.

Provenance & Evidence