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7h-pyrrolo[2,3-d]pyrimidine derivatives

A technology for drugs and compounds, applied in the field of 7H-pyrrolo[2,3-d]pyrimidine derivatives, can solve the problems of low specificity, low bioavailability, large toxic and side effects, etc., and achieve broad market prospects. Effect

Active Publication Date: 2019-07-26
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, although there are many drugs for the treatment of lung cancer on the market, they all have various defects, such as low bioavailability, low specificity, and large toxic and side effects.
These defects are often caused by the structural characteristics of the compound itself and its target, and it is difficult to overcome it in further research and development.

Method used

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  • 7h-pyrrolo[2,3-d]pyrimidine derivatives
  • 7h-pyrrolo[2,3-d]pyrimidine derivatives
  • 7h-pyrrolo[2,3-d]pyrimidine derivatives

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] The preparation of embodiment 1 key intermediate of the present invention

[0043] (1) Preparation of 5-iodo-4-amino-7H-pyrrolo[2,3-d]pyrimidine

[0044]

[0045] Weigh 4-amino-7H-pyrrolo[2,3-d]pyrimidine (0.60g, 4.47mmol) and N-iodosuccinimide (1.51g, 6.71mmol) and dissolve in 100ml acetonitrile, and dissolve at 120 Heating at reflux for 24h. After the reaction was completed, the solvent was evaporated, mixed with dichloromethane and water for extraction, the organic phase was dried over anhydrous sodium sulfate, evaporated under reduced pressure, separated and purified by column chromatography to obtain 0.96 g of a yellow solid (yield 82.51%).

[0046] 1 H NMR(500MHz,DMSO-d6)δ13.78(s,1H),8.17(s,1H),7.09(bs,2H).HR-MS(ESI+): Calc.for[C 6 h 5 IN 4 ]:260.9592[M+H]+,found:260.9638[M+H]+,282.9458[M+Na]+.

[0047] (2) Preparation of 5-iodo-7-n-butyl-7H-pyrrolo[2,3-d]pyrimidine 4-amino

[0048]

[0049] Weigh 5-iodo-4-amino-7H-pyrrolo[2,3-d]pyrimidine (2g, 0.0077mo...

Embodiment 2

[0051] Example 2 Preparation of 4-(4-amino-7-n-butyl-7H-pyrrolo[2,3-d]pyrimidine-5-)phenol (compound 1)

[0052]

[0053] 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (660 mg, 3.0 mmol) was added to 5-iodo-7-n-butyl After adding base-7H-pyrrolo[2,3-d]pyrimidine 4-amino (177mg, 0.56mmol) in 1,4-dioxane / water (5:1, 25mL:5mL) solution, continue to add carbonic acid Potassium (41.4mg, 3.0mmol) and PdCl 2 (dppf) (4 mg, 0.05 mmol). It was then heated in an oil bath at 90°C for 24 hours. Water and ethyl acetate were added for extraction, and the organic layer was dried over anhydrous magnesium sulfate and evaporated under reduced pressure to obtain 100 mg of white solid (yield 75%).

[0054] 1 H NMR (600MHz, Chloroform-d) δ8.25(s, 1H), 7.55-7.05(d, J=7.4Hz, 4H), 7.01(s, 1H), 6.99(s, 1H), 5.36(s, 2H), 4.26-4.23(t, J=7.2Hz, 2H), 1.89-1.83(m, 2H), 1.41-1.36(m, 2H), 0.89-0.87(d, 3H).HR-MS(ESI+) : Calc.for[C 16 h 18 N 4 O]: 283.1514[M+H]+; Found 283.1552[M+H]+, 305.13...

Embodiment 3

[0055] Example 3 Preparation of 2-(2-(2-(2-(4-(4-amino-7-n-butyl-7H-pyrrolo[2,3-d]pyrimidine-5-)phenoxy)ethyl Oxy)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonic acid (Compound 2)

[0056]

[0057] Tetraethylene glycol bis(p-toluene hydrochloride) (164mg, 3.46mmol), 4-(4-amino-7-n-butyl-7H-pyrrolo[2,3-d]pyrimidine-5-)phenol (100mg , 3.46mmol), and anhydrous potassium carbonate (100mg, 3.46mol) were heated at reflux in 50mL benzene solution for 4h, after neutralization with 1N HCl, the reaction mixture was extracted with dichloromethane. The solution was then dried under reduced pressure to obtain a solid, which was separated by column chromatography to obtain 160 mg of a brown-yellow syrupy product (yield 76%).

[0058] 1 H NMR (600MHz, Chloroform-d)δ8.29(s,1H),δ7.84-6.97(m,8H,arom-H),6.95(s,1H),5.52(s,2H),4.23-4.21 (t,J=7.2Hz,2H),4.23-3.59(t,J=7.2Hz,16H),δ2.44(s,3H),1.87–1.80(m,2H),1.44–1.35(m,2H ),0.97-0.95(t,J=7.4Hz,3H).HR-MS(ESI+): Calc.for[C 31 h 40 N 4 o 7 S]: 613...

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Abstract

Disclosed is a 7H-pyrrolo[2,3-d]pyrimidine derivative as represented by formula (I). The compound provided by the present invention has a remarkable inhibitory effect on tumour cells and can be used for preventing and / or treating tumour-related diseases, especially lung cancer, and has wide application prospects.

Description

technical field [0001] The present invention relates to 7H-pyrrolo[2,3-d]pyrimidine derivatives. Background technique [0002] At present, lung cancer is one of the malignant tumors with the fastest increasing morbidity and mortality and the greatest threat to the health and life of the population. [0003] However, although there are many drugs for treating lung cancer on the market, they all have various defects, such as low bioavailability, low specificity, and large toxic and side effects. These defects are often caused by the structural characteristics of the compound itself and its target, which are difficult to overcome in further research and development. [0004] Therefore, those skilled in the art hope to synthesize a variety of compounds with different structures and explore new targets to overcome the aforementioned defects. Contents of the invention [0005] To solve the above problems, the present invention provides a 7H-pyrrolo[2,3-d]pyrimidine derivative ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/04A61K31/519A61P35/00A61P11/00
CPCC07D487/04
Inventor 何杨柴莹莹陈勃江周兴龙李长富邱志新李为民
Owner WEST CHINA HOSPITAL SICHUAN UNIV