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Synthetic method of 2-(3,3,3-trifluoropropylthio) adenosine

A technique for the synthesis of trifluoropropylthio, which is applied in the field of synthesis of 2-adenosine, which can solve the problems of unmonitorable hydrolysis reaction, low yield of ring-closing reaction, numerous reaction steps, etc., achieving low cost and simplified synthesis route , the effect of a simple route

Inactive Publication Date: 2017-07-07
GROWINGCHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this reaction route, the hydrolysis reaction cannot be monitored, and the yield of the ring-closing reaction is very low, resulting in an extremely low overall yield; the reaction steps are numerous, the handling is troublesome, and the reaction time is too long

Method used

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  • Synthetic method of 2-(3,3,3-trifluoropropylthio) adenosine
  • Synthetic method of 2-(3,3,3-trifluoropropylthio) adenosine
  • Synthetic method of 2-(3,3,3-trifluoropropylthio) adenosine

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Experimental program
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Embodiment 11

[0035] The preparation of embodiment 1.1 formula (II) compound

[0036] Under an ice-water bath, in a 50mL single-necked bottle, add 0.4g (1.0eq) of the raw material formula (I) 2-chloroadenine, 1.5g (2.0eq) of ribose, and 5mL of nitromethane, and the system becomes a yellow suspension , adding SnCl 4 0.62g (1.0eq), the temperature was slowly raised to room temperature, and the stirring was continued for 3 hours. Thin-layer chromatography detected that the reaction was complete.

[0037] Add 20 mL of ethyl acetate, add saturated aqueous sodium bicarbonate solution to wash, and dry the ethyl acetate, evaporate it to dryness and pass through the column (eluent: ethyl acetate:petroleum ether at 1:1) to obtain a light yellow solid compound of formula (II) 0.82g, yield 81%.

[0038] The NMR data are as follows:

[0039] 1 H NMR (400MHz, CDCl 3 )δ7.97(s,1H),6.75(s,2H),6.18(d,J=5.6Hz,1H),5.81(t,J=5.6Hz,1H),5.68–5.57(m,1H), 4.44(s,1H),4.41(s,2H),2.43(s,1H),2.15(d,J=6.1Hz,3H),2.1...

Embodiment 12

[0041] The preparation of embodiment 1.2 formula (II) compound

[0042] Under an ice-water bath, in a 50mL single-necked bottle, add 0.4g (1.0eq) of the raw material formula (I) 2-chloroadenine, add 1.5g (2.0eq) of ribose, add 5mL of tetrahydrofuran, the system is a yellow suspension, add SnCl 4 0.62g (1.0eq), the temperature was slowly raised to room temperature, and the stirring was continued for 3 hours. Thin-layer chromatography detected that the reaction was complete.

[0043] Add 20 mL of ethyl acetate, add saturated aqueous sodium bicarbonate solution to wash, and dry the ethyl acetate, evaporate it to dryness and pass through the column (eluent: ethyl acetate:petroleum ether at 1:1) to obtain the compound of formula (II) as light yellow solid 0.69g, yield 68%.

[0044] The NMR data are as follows:

[0045] 1 H NMR (400MHz, CDCl 3 )δ7.97(s,1H),6.75(s,2H),6.18(d,J=5.6Hz,1H),5.81(t,J=5.6Hz,1H),5.68–5.57(m,1H), 4.44(s,1H),4.41(s,2H),2.43(s,1H),2.15(d,J=6.1Hz,3H),2.13(d...

Embodiment 13

[0047] The preparation of embodiment 1.3 formula (II) compound

[0048] Under an ice-water bath, add 0.4g (1.0eq) of the raw material formula (I) 2-chloroadenine, 1.5g (2.0eq) of ribose, and 5mL of nitromethane into a 50mL single-necked bottle, and the system becomes a yellow suspension , adding SnCl 4 0.62g (0.5eq), the temperature was slowly raised to room temperature, and the stirring was continued for 3 hours. Thin-layer chromatography detected that the reaction was complete.

[0049] Add 20 mL of ethyl acetate, add saturated aqueous sodium bicarbonate solution to wash, and dry the ethyl acetate, evaporate it to dryness and pass through the column (eluent: ethyl acetate:petroleum ether at 1:1) to obtain the compound of formula (II) as light yellow solid 0.53g, yield 52.5%.

[0050] The NMR data are as follows:

[0051] 1 H NMR (400MHz, CDCl 3 )δ7.97(s,1H),6.75(s,2H),6.18(d,J=5.6Hz,1H),5.81(t,J=5.6Hz,1H),5.68–5.57(m,1H), 4.44(s,1H),4.41(s,2H),2.43(s,1H),2.15(d,J=6.1Hz...

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Abstract

The invention belongs to the field of medicinal chemistry synthesis and discloses a synthetic method of 2-(3,3,3-trifluoropropylthio) adenosine. The method comprises the following steps: firstly performing nucleophilic substitution between 2-Chloroadenine (as shown in a formula I) as a raw material and tetraacetylribofuranose in a first solvent under a function of catalyst SnCl4 to obtain a compound (as shown in a formula II); performing hydrolysis reaction on the compound (as shown in the formula II) in a second solvent under a function of alkali a to obtain a compound (as shown in formula a III); finally performing nucleophilic substitution on the compound (as shown in the formula III) and 3,3,3-trifluoro-propanethiol under a function of alkali b to obtain a compound (as shown in a formula IV), namely 2-(3,3,3-trifluoropropylthio) adenosine. The synthetic method in the invention is simple in lines, high in yield and low in cost, and raw materials are low in cost and easy to obtain.

Description

technical field [0001] The invention relates to a method for synthesizing 2-(3,3,3-trifluoropropylthio)adenosine, which can be used as P2Y 12 Antagonist anti-platelet aggregation drug cangreno important intermediate, belonging to the synthetic field of medicinal chemistry. Background technique [0002] Cardiovascular disease has become the leading cause of death and disability worldwide. According to World Bank statistics, by 2030, the number of myocardial infarction patients in my country will reach 23 million, which will bring a heavy social and economic burden. Antiplatelet drugs are an important cornerstone in the treatment of acute myocardial infarction, among which P2Y 12 Antagonist antiplatelet aggregation drugs have become a research hotspot in recent years. Cangreno as first IV class of P2Y 12 Antagonist drugs are the focus of research. The synthetic method of the main intermediate 2-(3,3,3-trifluoropropylthio) adenosine of cangreno reported in the literature i...

Claims

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Application Information

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IPC IPC(8): C07H19/167C07H1/00
CPCC07H19/167C07H1/00
Inventor 肖锋罗宇占莉罗恬
Owner GROWINGCHEM
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