4-Methylmorpholine → (S)-3-cyclohexyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid (Example 7, step 2) (150 mg, 0.40 mmol), in tetrahydrofuran (5 mL) was treated with commercially available N-methylmorpholine (0.11 mL, 1.01 mmol), 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU) (384 mg, 1.01 mmol) and 1-((R)-2,3-diethoxy-propyl)-1H-pyrazol-3-ylamine (96 mg, 0.48 mmol) (prepared following the procedure described in WO2009127546). The mixture was heated in a sealed tube was heated for 24 hours at 90° C. The reaction mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue, upon silica gel flash chromatography using hexane-ethyl acetate gradient elution, afforded (S)-3-cyclohexyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide (145 mg, 65.3%), as a white solid.

Provenance & Evidence