Fluorinated 2-arylbenzo heterocyclic compound with high affinity to Aβ 946; plaques and containing chiral side chain substituent, and preparation method and usage thereof

A preparation method of a compound shown as Formula (I):

• wherein X is N;
• Y is S;
• Z is N;
• R1 is
• F in R1 is 18F;
• and R2 is N(CH3)2,
• wherein the preparation method of the compound consists of steps of:
• (1) dissolving 1 mmol of
• in 30 mL of anhydrous ethanol and adding 0.3 mL of a 200 g/L NaOH solution to a mixture thereof, wherein X is N;
• Y is S;
• Z is N;
• R is N(CH3)2;
• stirring the mixture in an oil bath at 80° C. until reflux lasts for 1 h;
• adding 1.5 mmol of
• to the mixture;
• after reaction is completed, removing a solvent;
• wherein after column chromatography separation, a compound with a Formula (VI) shown below is obtained:
• (2) when R is NHCH3, dissolving 1 mmol of the compound with the Formula (VI), 8 mmol of imidazole and 8 mmol of tert-butyldimethylsilyl chloride in 30 mL of a CH2Cl2 solution;
• stirring a mixture thereof in an oil bath at 40° C. until reflux lasts for 5 h;
• after reaction is completed, removing CH2Cl2;
• wherein after the column chromatography separation, a compound with a Formula (VIII) shown below is obtained:
• (3) dissolving 1 mmol of the compound with the Formula (VIII) in 30 mL of a THF solution and adding an excessive dose of (Boc)2O (Di-tert-butyl decarbonate) to a mixture thereof;
• stirring the mixture in an oil bath at 80° C. until reflux lasts for a night;
• after reaction is completed, removing the THF;
• wherein after the column chromatography separation, a compound with a Formula (XI) shown below is obtained:
• (4) dissolving 1 mmol of the compound with the Formula (XI) in 30 mL of the THF solution and adding 7 mmol of TBAF to a mixture thereof;
• stirring the mixture in an oil bath at 30° C. until reflux lasts for one night;
• after reaction is completed, removing the THF;
• wherein after the column chromatography separation, a compound with a Formula (XII) shown below is obtained:
• (5) dissolving 1 mmol of the compound with the Formula (VI) and 1 mmol of the compound with the Formula (XII) in 5 mL of pyridine respectively and adding 1.5 mmol of TsCl to a mixture thereof;
• stirring the mixture in an ice bath at 0° C. until reactions occur;
• after the reactions are completed, removing the pyridine;
• wherein after the column chromatography separation, a compound with a Formula (XV) shown below is obtained:
• wherein X is N;
• Y is S;
• Z is N;
• R is N(CH3)2;
• (6) dissolving 1 mmol of the compound with the Formula (XV), 4 mmol of 3,4-dihydro-2H-pyran and 0.2 mmol of PPTS (Pyridinium p-toluenesulfonate) in 30 mL of a CH2Cl2 solution respectively;
• stirring a mixture thereof in an oil bath at 40° C. until reflux lasts for a night;
• after reaction is completed, removing CH2Cl2;
• wherein after the column chromatography separation, a compound with a Formula (XVII) shown below is obtained:
• and
• (7) dissolving 10 mg of the compound with the Formula (XVII) in 2 mL of acetonitrile;
• adding a mixture thereof to a reaction tube of dehydrated 18F− and K222/K2CO3;
• maintaining labeling at 100° C. for 12 min;
• after the mixture is cooled, adding 0.15 mL of 1M HCl;
• after swirling is completed, keeping reacting for 5 min;
• after the mixture is cooled, adding a small amount of water and neutralizing the mixture with NaHCO3 until the mixture is alkaline;
• separating the mixture with a C18 reverse phase column and rinsing the mixture with water to remove salts and residual 18F−;
• then rinsing the mixture with the acetonitrile;
• after the mixture is dried with N2, separating with HPLC to obtain a compound with a Formula (XIV) shown below: