Preparation method of formaldehyde-substituted aza-condensed ring compound
A compound and fused ring technology, applied in the field of organic compound synthesis, can solve the problems of low conversion rate and yield, harsh reaction conditions, difficult separation and purification, etc., and achieve high conversion rate and yield, low post-processing energy consumption, and route Good repeatability of steps
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Embodiment 1
[0080] The preparation of embodiment 1,5-fluoroisoquinoline-1-formaldehyde
[0081]
[0082] Synthesis of step 1, 1-chloro-5-fluoroisoquinoline: 5-fluoroisoquinolin-1(2H)-ketone (450mg) was added to phosphorus oxychloride (8mL), and then the reaction system was heated at 80 The reaction was stirred at °C for 2 hours. After the reaction was completed, the solvent was concentrated and removed, the reaction residue was dissolved in dichloromethane and washed with saturated sodium bicarbonate solution, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to remove the solvent to obtain a white solid compound 1- Chloro-5-fluoroisoquinoline (480mg, yield 96%), this product can be directly used in the next step without purification;
[0083] Synthesis of step 2, 5-fluoro-1-methylisoquinoline: dry tetrahydrofuran (8mL), compound 1-chloro-5-fluoroisoquinoline (480mg), dimethyl zinc (1mol / L, 12.2 mL) and tetrakis(triphen...
Embodiment 2
[0088] The preparation of embodiment 2,6-fluoroisoquinoline-1-formaldehyde
[0089]
[0090] Synthesis of step 1, 1-chloro-6-fluoroisoquinoline: 6-fluoro-isoquinolin-1 (2H)-one (600mg) was added to phosphorus oxychloride (6mL), and then the reaction system was The reaction was stirred at 80°C for 2 hours. After the reaction was completed, the solvent was concentrated and removed, the reaction residue was dissolved in dichloromethane and washed with saturated sodium bicarbonate solution, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to remove the solvent to obtain a white solid crude compound 1 -Chloro-6-fluoroisoquinoline (650 mg, yield 97%), this product was directly used in the next step without purification.
[0091] Synthesis of step 2, 6-fluoro-1-methylisoquinoline: dry tetrahydrofuran (20mL), compound 1-chloro-6-fluoroisoquinoline (550mg), dimethyl zinc (1mol / L, 12.1 mL) and tetrakis(triphenylphosp...
Embodiment 3、8
[0096] The preparation of embodiment 3,8-fluoroisoquinoline-1-formaldehyde
[0097]
[0098] Synthesis of step 1, 1-chloro-8-fluoroisoquinoline: 8-fluoroisoquinolin-1(2H)-ketone (250mg) was added to phosphorus oxychloride (3.2mL), and then the reaction system was The reaction was stirred at 80°C for 2 hours. After the reaction was completed, the solvent was concentrated and removed, the reaction residue was dissolved in dichloromethane and washed with saturated sodium bicarbonate solution, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to remove the solvent to obtain a white solid crude compound 1 -Chloro-8-fluoroisoquinoline) (198 mg, yield 73%), this product was directly used in the next step without purification.
[0099] The synthesis of step 2,8-fluoro-1-methylisoquinoline: dry tetrahydrofuran (8mL), compound 1-chloro-8-fluoroisoquinoline (198mg), dimethyl zinc (1mol / L, 4.0 mL) and tetrakis(triphenyl...
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