A kind of synthetic method of olanzapine related substance compound i and compound ii
A technology related to substances and synthetic methods, applied in the direction of organic chemistry, etc., can solve the problems of not providing the preparation methods of compounds I and II, and the synthesis of no compounds, achieving significant technical and economic benefits, reliable material guarantee, and high total yield. Effect
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[0032] Synthetic method of the present invention comprises the following steps:
[0033] S1. Synthesis of compound I: add olanzapine, organic solvent and water into the reaction flask, add Oxone and sodium hydroxide in sequence, and continue the reaction until the olanzapine spots disappear, and then adjust the pH of the system to 6-7, After extraction and recrystallization, compound I was obtained;
[0034] S2: Synthesis of Compound II: Dissolve Compound I in an organic solvent, add inorganic lye at 0°C, then add acetyl chloride, continue to stir the reaction at 0°C until Compound I disappears, separate and extract, pass through a silica gel column Purification by chromatography affords compound II.
[0035] In some preferred embodiments, in the step S1, the organic solvent is selected from one or more of methanol, ethanol, dichloromethane, chloroform, N,N-dimethylformamide or N-methylpyrrolidone Mixed solvents. Most preferred is N,N-dimethylformamide.
[0036] In some pr...
Embodiment 1
[0051] Embodiment 1 of the present invention provides a kind of preparation method of compound I, and its synthetic route is as follows:
[0052]
[0053] Specifically adopt the following method to prepare:
[0054]Add olanzapine (8.0g, 25.6mmol), N,N-dimethylformamide (40mL) and water (80mL) into the reaction flask, add Oxone (7.9g, 25.6mmol) under stirring, continue to Stir at 25°C for 2h, then add solid sodium hydroxide (3.1g, 76.8mmol), continue stirring at 25°C for 1h, TLC detects that the starting material disappears. Use 2M hydrochloric acid to adjust the pH of the system to 6-7, add dichloromethane (120 mL) to the reaction liquid, separate and extract, and wash the organic layer with water (50 mL×3) and saturated brine (50 mL×3) successively. The organic layer was dried with anhydrous sodium sulfate, filtered with suction, and the filtrate was distilled off under reduced pressure. The crude product was recrystallized from acetonitrile (55 mL) to obtain the pure com...
Embodiment 2
[0061] Embodiment 2 of the present invention provides a kind of preparation method of compound I:
[0062] Add olanzapine (6.0g, 19.2mmol), N-methylpyrrolidone (30mL) and water (60mL) into the reaction flask, and add under stirring (5.9g, 19.2mmol), continue to stir at 25°C for 2h after the addition, then add solid sodium hydroxide (2.3g, 57.6mmol), continue to stir at 25°C for 1h, TLC detects that the starting material disappears. Use 2M hydrochloric acid to adjust the pH of the system to 6-7, add dichloromethane (90 mL) to the reaction solution, separate and extract, and wash the organic layer with water (40 mL×3) and saturated brine (40 mL×3) successively. The organic layer was dried with anhydrous sodium sulfate, filtered with suction, and the filtrate was evaporated under reduced pressure. The crude product was recrystallized from acetonitrile (41 mL) to obtain pure compound I.
[0063] Using this method, 4.6 g of a light yellow solid was prepared, with a yield of 79.2%...
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