Stage #1: 4-boronopyridine-2-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl acetamide at 20℃; for 0.666667h;
Stage #2: Cyclopropylamine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 20℃; for 3h;
24.1 Step 1 - Preparation of [2-(cyclopropylcarbamoyl)-4-pyridyl]boronic acid (141)
To a round bottom flask were added 4-boronopyridine-2-carboxylic acid 139 (120 mg, 0.72 mmol), l-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.28 g, 1.44 mmol), and 1- hydroxybenzotriazole (0.19 g, 1.44 mmol) in dimethylacetamide (3 ml). The mixture was stirred at room temperature for 40 minutes, then added cyclopropanamine (0.06 ml, 1.44 mmol) followed by N,N- diisopropylethylamine (0.25 ml, 1.44 mmol). The reaction mixture was stirred at room temperature for three hours, poured into water and extracted with ethyl acetate. The organic layer was washed by brine and dried under sodium sulfate. After removal of drying agent and solvent, the residue was dried under vacuum to provide compound 141 (60 mg, 40.5%). The compound was used for the subsequent reaction without purification.