Pyrrolidine → (NZ)-N-[5-methyl-3-(2,2,3,3-tetrafluoro-1,4-benzodioxin-6-yl)-1,3-thiazol-2-ylidene]pyrrolidine-1-carboxamide

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Reaction Conditions

Reaction Steps

A solution of Example 22C (290 mg, 0.90 mmol) in CH2Cl2 (4.0 mL, 0.2 M) was added dropwise over 17 minutes to a −78° C. solution of 20% phosgene/toluene (630 μL, 1.2 mmol) in CH2Cl2 (5.0 mL, 0.2M). The mixture was stirred cold for 10 minutes after which diisopropylethylamine (140 μL, 0.80 mmol) was added dropwise over 3 minutes. The mixture was stirred cold for 45 minutes and allowed to warm to −20° C. over 1 hour; then allowed to warm to ambient temperature. After 1 hour at ambient temperature, pyrrolidine (135 μL, 1.6 mmol) was added and the mixture was stirred for 16 hours. To the solution was added more pyrrolidine (90 μL, 1.1 mmol), the mixture was stirred for 20 minutes, diluted with concentrated aqueous NH4OH (2 mL) and stirred for 5 minutes. The aqueous phase was separated and extracted with CH2Cl2 (3×). The combined organic phases were dried with Na2SO4, concentrated under reduced pressure, and chromatographed on Alltech silica eluting with 0-10% Et2O in 1:1 CH2Cl2/hexanes to provide the titled compound. 1H NMR (CD2Cl2) δ ppm 1.83 (m, 4H), 2.24 (d, 3H), 3.36 (m, 2H), 3.40 (m, 2H), 6.66 (d, 1H), 7.25 (d, 1H), 7.42 (dd, 1H), 7.54 (d, 1H); MS (ESI) 418 (M+H).

Provenance & Evidence