Method for synthesizing positive electron radioactive imaging agent labeled precursor thymidine derivative

A technology of thymidine derivatives and synthetic methods, which is applied in the field of chemical synthesis, can solve the problems of complex operation, high cost, and long cyclization reaction time, and achieve the effect of simple operation, low cost, and short reaction time

Inactive Publication Date: 2009-07-15
GUANGZHOU GENERAL HOSPITAL OF GUANGZHOU MILITARY COMMAND
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  • Description
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Problems solved by technology

[0008] Documents [4] and [5] use 5'-O-(4,4'-dimethoxytrityl)-thymidine as raw materials to synthesize products through two-step reactions, but the raw materials used in this method Compared with thymidine, the cost is higher, and the cyclization reaction time is as long as three days; the literature [3] has improved the synthesis method, but the operation is still complicated and requires heating and reflux, and the 5'-O- (4,4'-dimethoxytrityl)-thymidine as raw material

Method used

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  • Method for synthesizing positive electron radioactive imaging agent labeled precursor thymidine derivative
  • Method for synthesizing positive electron radioactive imaging agent labeled precursor thymidine derivative
  • Method for synthesizing positive electron radioactive imaging agent labeled precursor thymidine derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] (1) Dissolve 1.5 g (6 mmol) of thymidine in 25 mL of anhydrous pyridine, stir magnetically, add 2.54 g (7.5 mmol) of 4,4'-dimethoxytrityl chloride under nitrogen protection, and (20-25°C) to react for 2 hours.

[0028] (2) The mixture was cooled to 0°C, and 1.16ml (15mmol) of methanesulfonyl chloride was added, then the temperature of the mixture was raised to room temperature (20-25°C), and magnetically stirred for 2 hours.

[0029] (3) The mixture was concentrated to dryness by rotary evaporation, the residue was dissolved in 60 mL of dichloromethane, 20 mL of 1% aqueous sodium hydroxide solution (w / v) was added, stirred well, and reacted for 30 minutes.

[0030] (4) Take the dichloromethane layer, wash with water 3 times and collect the organic phase. The organic phase was dried by adding anhydrous sodium sulfate, concentrated, and separated by silica gel column chromatography (eluent: ethyl acetate: n-hexane = 3: 1) to obtain 2.36 g of a white solid with a yield of...

Embodiment 2

[0032] (1) Dissolve 1.5 g (6 mmol) of thymidine in 30 mL of anhydrous pyridine, stir magnetically, and add 2.54 g (7.5 mmol) of 4,4'-dimethoxytrityl chloride under nitrogen protection, 30 °C for 3 hours.

[0033] (2) The mixture was cooled to 0° C., 1.16 ml (15 mmol) of methanesulfonyl chloride was added, and then the temperature of the mixture was raised to 30° C., and magnetically stirred for 3 hours.

[0034](3) Concentrate the mixture to dryness by rotary evaporation, dissolve the residue in 60 mL of dichloromethane, add 30 mL of 10% aqueous sodium bicarbonate solution, stir well, and react for 30 minutes.

[0035] (4) Take the dichloromethane layer, wash with water 3 times and collect the organic phase. The organic phase was dried by adding anhydrous sodium sulfate, concentrated, and separated by silica gel column chromatography (eluent: ethyl acetate: n-hexane = 3: 1) to obtain 2.81 g of a white solid with a yield of 89% and a purity of more than 98% ( high performance...

Embodiment 3

[0037] (1) Take thymidine 1.5g (6mmol) and dissolve it in 30mL anhydrous pyridine, stir it magnetically, add 4,4'-dimethoxytrityl chloride 3.05g (9mmol) under the protection of nitrogen, room temperature ( 20~25°C) for 3 hours.

[0038] (2) Cool the mixture to 0°C, add 1.55ml (20mmol) of methanesulfonyl chloride, then raise the temperature of the mixture to room temperature (20-25°C), and stir magnetically for 3 hours.

[0039] (3) The mixture was concentrated to dryness by rotary evaporation, the residue was dissolved in 50 mL of ethyl acetate, 25 mL of 20% sodium carbonate aqueous solution was added, fully stirred, and reacted for 45 minutes.

[0040] (4) Take the ethyl acetate layer, wash with water for 3 times and collect the organic phase. The organic phase was dried by adding anhydrous sodium sulfate, concentrated, and separated by silica gel column chromatography (eluent: ethyl acetate: n-hexane = 3: 1) to obtain 1.93 g of a white solid with a yield of 61% and a purity...

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Abstract

The invention discloses a synthetic method of a labelled precursor of a positron emission developer (a thymidine derivative), in particular relates to a synthetic method of 5'-O-(4,4'-dimethoxytriphenylmethyl)-2,3'-anhydro-thymidine. The synthetic method comprises the following steps: thymidine is taken as a raw material for reacting with 4,4'-dimethoxytriphenylmethyl and methylsulfonyl chloride, an intermediate product is subject to a cyclization reaction in alkaline aqueous solution, and finally separated and purified to obtain a final product. The synthetic method has the advantages of low-cost raw materials, simple operation, few process steps, short reaction time and high product yield.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, in particular to a positron radioactive imaging agent labeled precursor thymidine derivative 5'-O-(4,4'-dimethoxytrityl)-2,3'- Synthetic method of dehydrothymidine. technical background [0002] 3'-deoxy-3'-[ 18 F] Fluorothymidine (3'-Deoxy-3'-[ 18 F]fluorothymidine, [ 18 F]FLT) is a radioactive imaging agent for positron emission tomography (position emission tomography, PET). [ 18 F]FLT can non-invasively detect cell proliferation status in vitro, which is of great value in the diagnosis, differentiation and curative effect monitoring of tumors. Depending on the type of labeled precursor, [ 18 F]FLT preparation methods are mainly divided into two types, and the labeling precursors used are 3-N-tert-butoxycarbonyl-[5'-O-(4,4'-dimethoxytrityl)- 2-deoxy-3'-O-(4-nitrobenzenesulfonyl)-β-D-furan threo five-membered glycosyl]thymine (3-N-Boc-1-[5-O-(4, 4'-dimethoxytrityl)-3-O-nitrophenylsulfo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H19/073C07H1/00A61K51/04A61K101/02
Inventor 邓伟杰尹吉林张相年周崝孙智平赵树进
Owner GUANGZHOU GENERAL HOSPITAL OF GUANGZHOU MILITARY COMMAND
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