Example 113 Steps for the synthesis of 10-(4-piperidin-1-ylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazine-3-carboxamide A. Preparation of 4-piperidin-1-ylbenzylcarbonitrile: Under nitrogen protection, 4-fluorobenzylcarbonitrile (1 g, 8.26 mmol), piperidine (0.90 mL, 9.08 mmol), piperidine (0.90 mL, 9.08 mmol) and anhydrous potassium carbonate (2.28 g, 16.51 mmol) were dissolved in anhydrous 1-methyl-2-pyrrolidinone (10 mL), and the reaction was stirred for 20 h at 120°C. The reaction was carried out under nitrogen protection. After completion of the reaction, the mixture was cooled to room temperature, diluted with water (100 mL) and extracted with ethyl acetate (100 mL). The organic phases were combined, washed sequentially with water (100 mL) and saturated saline (100 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give an orange oily crude product. It was purified by fast column chromatography using a gradient elution of hexane with ethyl acetate (1% to 7%) to give the orange oily product, which was further crystallized from hexane to give 4-(1-piperidinyl)benzonitrile (1.41 g, 92% yield) as an orange crystalline solid with a melting point of 54°C. Mass spectrum ((+)ESI, m/z): 187 [M+H]+. Elemental analysis (C12H14N2) Calculated values: C, 77.38; H, 7.58; N, 15.04. Measured values: C, 77.30; H, 7.41; N, 15.06.
