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2-phosphonyl-3-fluoro vinyl indole compound and preparation method thereof

A technology of fluorovinyl indole compound and difluoromethyl indole carbinol, which is applied in the field of 2-phosphono-3-fluorovinyl indole compound and preparation thereof, can solve harsh anhydrous and anoxic conditions, Difficulty in synthesizing raw materials, expensive photosensitizers, etc., to achieve a wide range of applicable substrates, green reaction solvents, and good compatibility.

Active Publication Date: 2021-04-30
NANJING FORESTRY UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are many synthetic methods for 2-phosphonoindole, such as the cyclization reaction of diisocyanostyrene and diphenoxyphosphine under photocatalytic conditions (Org. Lett. 2018, 20, 2382-2385), indole and The radical addition C2 phosphonylation reaction of diphenylphosphine oxide compounds under the action of silver catalyst and excess oxidant (Adv.Synth.Catal.2016,358,1753–1758), o-iodoaniline and phosphine oxide substituted alkyne in the transition Coupling cyclization reaction (Org.Lett.2010,12,1476-1479) under metal catalysis, etc., but there are many problems in these prior art methods, for example, need to use expensive photosensitizer, expensive Metal catalysts, excessive oxidants, etc., and many methods still have raw materials that are difficult to synthesize and reactions that require harsh anhydrous and oxygen-free conditions, etc.

Method used

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  • 2-phosphonyl-3-fluoro vinyl indole compound and preparation method thereof
  • 2-phosphonyl-3-fluoro vinyl indole compound and preparation method thereof
  • 2-phosphonyl-3-fluoro vinyl indole compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] The reaction formula is:

[0038]

[0039] A kind of synthetic method of 2-phosphono-3-fluorovinylindole compound: get 25mL round bottom flask, add difluoromethyl indole carbinol 2a (0.4mmol), diphenoxyphos 3a (0.6mmol), 95% ethanol (1 ml), stirred and reacted at 80°C for 6h, after the reaction was completed, cooled to room temperature, concentrated the reaction solution by rotary evaporation, and separated by silica gel column chromatography (eluent: ethyl acetate:petroleum ether=40: 60), the target product 1aa (161.0 mg, white solid, yield 92%) was obtained.

[0040] The proton nuclear magnetic resonance spectrum figure of the compound 1aa prepared in embodiment 1 is as follows figure 1 Shown; The carbon nuclear magnetic resonance spectrogram of the compound 1aa prepared in embodiment 1 is as figure 2 Shown; The nuclear magnetic resonance fluorine spectrogram of the compound 1aa prepared in embodiment 1 is as image 3 Shown; The nuclear magnetic resonance phosp...

Embodiment 2

[0043] The reaction formula is:

[0044]

[0045] A kind of synthetic method of 2-phosphono-3-fluorovinylindole compound: get 25mL round bottom flask, add difluoromethyl indole carbinol 2b (0.4mmol), diphenoxyphos 3a (0.6mmol), 95% ethanol (1 ml), stirred and reacted at 80°C for 24h, after the reaction was completed, cooled to room temperature, concentrated the reaction solution by rotary evaporation, and separated by silica gel column chromatography (eluent: ethyl acetate:petroleum ether=50: 50), the target product 1ba (161.4 mg, white solid, yield 89%) was obtained.

[0046] 1 H NMR (600MHz, DMSO-d 6 )δ11.15(s,1H),8.83(s,1H),7.70(dd,J=12.1,7.7Hz,4H),7.53(t,J=7.3Hz,2H),7.44(td,J=7.3 ,1.5Hz,4H),7.30(d,J=8.8Hz,1H),7.25-7.19(m,3H),7.14(d,J=7.0Hz,2H),6.91(t,J=84.1Hz,1H ),6.75(dd,J=8.8,1.7Hz,1H),6.29(d,J=1.3Hz,1H); 13 C NMR (150MHz, DMSO-d 6 )δ151.8, 148.0(d, J=275.5Hz), 134.8(d, J=2.0Hz), 133.2(d, J=10.1Hz), 133.1(d, J=106.8Hz), 132.4(d, J=2.2 Hz), 131.8(d, J=10.0Hz), 1...

Embodiment 3

[0048] The reaction formula is:

[0049]

[0050] A kind of synthetic method of 2-phosphono-3-fluorovinylindole compound: get 25mL round bottom flask, add difluoromethyl indole carbinol 2c (0.4mmol), diphenoxyphos 3a (0.6mmol), Ethanol (95%) (1 ml), stirred and reacted at 80°C for 12h, after the reaction was completed, cooled to room temperature, concentrated the reaction solution by rotary evaporation, and separated by silica gel column chromatography (eluent was ethyl acetate:petroleum ether= 50:50), the target product 1ca (168.5 mg, white solid, yield 85%) was obtained.

[0051] 1 H NMR (600MHz, CDCl 3 )δ10.75(s,1H),8.09(s,1H),7.97(dd,J=8.8,1.4Hz,1H),7.63-7.56(m,4H),7.50(d,J=8.7Hz,1H ),7.47(td,J=7.5,1.2Hz,2H),7.31(td,J=7.8,3.1Hz,4H),7.1-7.09(m,3H),7.05-7.01(m,2H),6.38( d,J=82.8Hz,1H),3.85(s,3H); 13 CNMR (150MHz, CDCl 3 )δ148.1(d, J=279.8Hz), 140.5(d, J=11.0Hz), 134.4(d, J=4.0Hz), 132.4, 132.0(d, J=10.8Hz), 131.0(d, J =112.0Hz), 129.2(d, J=12.1Hz), 128.5(d, J=7.1Hz...

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Abstract

The invention discloses a 2-phosphonyl-3-fluoro vinyl indole compound which is complex and diverse in structure, contains phosphonyl, an indole ring and fluoro vinyl, can be subjected to further structural modification and serves as an important intermediate for organic synthesis. After the phosphonyl is reduced into trivalent phosphine, the trivalent phosphine can also be used as an important phosphine ligand to participate in organic synthesis reaction catalyzed by transition metal and the like. According to the synthetic method of the 2-phosphonyl-3-fluoro vinyl indole compound, in the air atmosphere, a difluoromethyl indole methanol compound and a disubstituted phosphine oxide compound serve as raw materials and react in a solvent, and the method is simple, free of any catalyst, environmentally friendly, mild in reaction condition, high in yield and wide in reaction substrate range. The 2-phosphonyl-3-fluoro vinyl indole compound disclosed by the invention can be used as a ligand and an organic synthesis intermediate, and has a wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and specifically relates to a 2-phosphono-3-fluorovinylindole compound and a preparation method thereof. Background technique [0002] Indole and its derivatives are a very important class of alkaloids, which are widely distributed in nature. Indole compounds have very important applications in the fields of medicine, pesticides, functional materials, and plant essential oils. On the other hand, organic phosphine compounds are not only used as ligands and pesticides, but also widely used in medicine, fireproof materials and other fields. And 2-phosphonoindole compounds have very important applications in the field of medicine, such as non-nucleoside reverse transcriptase inhibitors in the treatment of HIV-1 showed excellent effect (J.Med.Chem.2011,54,392-395; TetrahedronLett.2007,48,6080–6083; J.Clin.Pharmacol.2009,49,1408–1417); In addition, 2-phosphono compounds are not only widely ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/572
CPCC07F9/5728
Inventor 饶卫东安镝桑静静胡睿陈继超冯丽
Owner NANJING FORESTRY UNIV
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