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Method for synthesizing chiral Tr*ger's base derivatives

A derivative and chiral technology, applied in the new synthesis field of chiral base derivatives, can solve the problem of high cost, and achieve the effects of short reaction time, simple post-processing and mild reaction conditions.

Inactive Publication Date: 2015-07-29
XUZHOU NORMAL UNIVERSITY +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The traditional methods to obtain chiral TB are chemical resolution and chromatographic methods, but these methods have many defects, such as not being able to obtain large-scale, high cost, etc.
[0005] So far, there is no efficient, economical, and environmentally friendly direct synthesis of highly optically active TB derivatives

Method used

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  • Method for synthesizing chiral Tr*ger's base derivatives
  • Method for synthesizing chiral Tr*ger's base derivatives
  • Method for synthesizing chiral Tr*ger's base derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 5,12-Dimethyl-3,10-diphenyl-bis-1H-pyrazole[b,f][4,5]-1,5-diazabicyclo[3.3.1]-2,6 -The synthesis of octadiene (TB1), its reaction formula is as follows:

[0040]

[0041] In a 25mL round bottom flask, add 5-amino-3-methyl-1-phenyl-1H-pyrazole (2mmol), paraformaldehyde (6mmol) and [Py-G] + [BF 4 ] - (2mL), under argon protection, 2.0mL trifluoroacetic acid was added dropwise, stirred at room temperature for 5h, after the reaction was complete (TLC tracking), 10mL distilled water was added, suction filtered, and the solid crude product was subjected to column chromatography V 石油醚 :V 乙酸乙酯 =5:1, TB1 is obtained. Yield: 83%. M.p.: 266-267°C, white solid. ee 99%, (determined by HPLC analysis Chiralcel OD-H column, IPA:hexane=15:85), retention time: t minor =7.79min,t major =13.45min. 1 H NMR (400MHz, DMSO-d 6 )δ7.95-7.97(d, J=8.4Hz, 4H), 7.49-7.53(m, 4H), 7.30-7.32(t, J=8.0Hz, 2H), 4.24-4.32(t, J=7.2Hz , 4H), 3.59 (d, J=15.6Hz, 2H), 1.97 (s, 6H). HRMS (ESI) m / z:...

Embodiment 2

[0043]5,12-bis(4-methyl-phenyl)-3,10-diphenyl-bis-1H-pyrazole[b,f][4,5]-1,5-diazabicyclo[3.3 .1]-2, the synthesis of 6-octadiene (TB2), its reaction formula is as follows:

[0044]

[0045] In a 25mL round bottom flask, add 5-amino-3-(4-methylphenyl)-1-phenylpyrazole (2mmol), paraformaldehyde (6mmol) and [Py-G] + [BF 4 ] - (2mL), under argon protection, 2.0mL trifluoroacetic acid was added dropwise, stirred at room temperature for 7h, after the reaction was complete (TLC tracking), 10mL distilled water was added, suction filtered, and the solid crude product was subjected to column chromatography V 石油醚 :V 乙酸乙酯 =5:1, TB2 is obtained. Yield: 83%. M.p.: 266-267°C, white solid. Yield: 83%. M.p.283-284°C, white solid. ee 99% (determined by HPLC analysis Chiralcel OD-H column, IPA: hexane = 15: 85), retention time: t minor =7.66min,t major =13.26min. 1 H NMR (400MHz, DMSO-d 6 )δ8.07-8.09(d, J=8.0Hz, 4H).7.60-7.64(m, 4H), 7.44-7.46(m, 6H), 7.23-7.25(d, J=8.0Hz, 4H), 4....

Embodiment 3

[0047] 5,12-bis(4-methoxy-phenyl)-3,10-diphenyl-bis-1H-pyrazole[b,f][4,5]-1,5-diazabicyclo[ 3.3.1]-2, the synthesis of 6-octadiene (TB3), its reaction formula is as follows:

[0048]

[0049] In a 25mL round bottom flask, add 5-amino-3-(4-methoxyphenyl)-1-phenylpyrazole (2mmol), paraformaldehyde (6mmol) and [Py-G] + [BF 4 ] - (2mL), under argon protection, 2.0mL trifluoroacetic acid was added dropwise, stirred at room temperature for 7h, after the reaction was complete (TLC tracking), 10mL distilled water was added, suction filtered, and the solid crude product was subjected to column chromatography V 石油醚 :V 乙酸乙酯 =5:1, TB3 is obtained. Yield: 73%. M.p.>300°C, white solid. ee 79% (determined by HPLC analysis Chiralcel OD-H column, IPA: hexane = 15: 85), retention time: t minor =8.73min,t major =16.67min. 1 H NMR (400MHz, DMSO-d 6 )δ8.01-8.03 (d, J=8.0Hz, 4H).7.53-7.57 (m, 4H), 7.36-7.44 (m, 6H), 6.93-6.95 (d, J=8.0, 4H), 4.71- 4.75(d, J=8.4Hz, 2H), 4.54(s, 2H), 3....

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Abstract

The invention relates to a new synthesis method of chiral Tr*ger's base derivatives. According to the synthesis method, a chiral ionic liquid, 1-pyridine-3,4,6-tri-acetyl glucopyranose tetrafluoroborate, with glucose being a chiral source, which is used as a catalyst, and a solvent undergo direct one-step catalytic synthesis to obtain the series of chiral Tr*ger's base derivatives. According to the invention, the novel sugar-containing chiral ionic liquid, 1-pyridine-3,4,6-tri-acetyl glucopyranose tetrafluoroborate, is used as a catalyst. The method provided by the invention is green and environmental friendly, is simple and economical, and can be adopted to efficiently prepare the Tr*ger's base derivatives with high yield and high optical purity by one step.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, in particular to chiral A new synthetic method for base derivatives. Background technique [0002] base (hereinafter referred to as TB) and its derivatives are a class of trivalent nitrogen chiral center and C 2 Axial chiral basic compounds, due to their special V-shaped structure and molecular rigidity, their racemates have received more and more attention in the fields of chemistry, biology and medicine, and have been used in molecular recognition, supramolecular Chemistry, bioorganic chemistry, asymmetric catalysis and other fields; and because it can interact with DNA and exhibit great biological activity, it can be developed into various important pharmaceutical intermediates. [0003] Chiral sugar-containing ionic liquids have both the advantages of chiral substances and ionic liquids, and are a new class of chiral ionic liquids in recent years. As a chiral source of ionic ...

Claims

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Application Information

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IPC IPC(8): C07D487/22C07H19/048C07H1/00B01J31/04
CPCY02P20/54
Inventor 宛瑜苑睿林伟吴翚
Owner XUZHOU NORMAL UNIVERSITY
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