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Aryl or heteroaryl compound containing difluoroalkyl substitution, preparation method and application

A difluoroalkyl and compound technology, applied in the preparation of carbon-based compounds, the preparation of hydroxyl compounds, the preparation of organic compounds, etc., can solve the problems of poor functional group compatibility, narrow substrate application range, harsh reaction conditions, etc. Good compatibility, low production cost and few reaction steps

Active Publication Date: 2022-06-21
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The technical problem to be solved by the present invention is to overcome the harsh reaction conditions, expensive catalysts, poor functional group compatibility, and the scope of application of substrates in the existing preparation methods of aryl or heteroaryl compounds containing difluoroalkyl substitutions. Narrow, poor broad-spectrum and other defects, and provide a difluoroalkyl-substituted aryl or heteroaryl compound, preparation method and application

Method used

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  • Aryl or heteroaryl compound containing difluoroalkyl substitution, preparation method and application
  • Aryl or heteroaryl compound containing difluoroalkyl substitution, preparation method and application
  • Aryl or heteroaryl compound containing difluoroalkyl substitution, preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0108]

[0109] Into a 25mL reaction tube, add 110mg (0.9mmol) phenylboronic acid, 6.6mg (5mol%, refers to the percentage of moles of 5-bromo-5,5'-difluoropentylbenzene) NiCl 2 · DME, 8 mg (5 mol%) 4,4'-d t Bubpy (4,4'-di-tert-butylbipyridine), 14.6 mg (20 mol%) DMAP, 166 mg (1.2 mmol) K 2 CO 3 , 4 mL of triglyme, injected with 157 mg (0.6 mmol) of 5-bromo-5,5'-difluoropentylbenzene, and after stirring at 80°C for 24 hours, the isolated yield was 92%. The purity was identified by hydrogen spectroscopy as greater than 95%. 1 H NMR (400MHz, CDCl 3 )δ7.48–7.38(m,5H),7.27(t,J=7.3Hz,2H),7.20–7.11(m,3H),2.58(t,J=7.6Hz,2H),2.21–2.07(m ,2H),1.68–1.59(m,2H),1.54–1.45(m,2H). 19 FNMR (376MHz, CDCl 3 )δ-95.5(t,J=16.2Hz,2F). 13 C NMR (125.7MHz, CDCl 3 )δ142.1,137.5(t,J=26.6Hz),129.5(t,J=1.5Hz),128.34,128.32,128.30,125.8,124.9(t,J=6.2Hz),123.0(t,J=242.1Hz) ,38.9(t,J=27.5Hz),35.7,31.1,22.2(t,J=4.0Hz).IR(thinfilm)ν max 3027,2934,1496,1452,1327cm -1 .MS(EI): m / z(%)260(M + ),240,...

Embodiment 2

[0111]

[0112] Into a 25mL reaction tube, add 178.2mg (0.9mmol) 4-phenylbenzeneboronic acid, 6.6mg (5mol%, refers to the percentage of moles of 5-bromo-5,5'-difluoropentylbenzene) NiCl 2 · DME, 8 mg (5 mol%) 4,4'-d t Bubpy (4,4'-di-tert-butylbipyridine), 14.6 mg (20 mol%) DMAP, 166 mg (1.2 mmol) K 2 CO 3 , 4 mL of triglyme, injected with 157 mg (0.6 mmol) of 5-bromo-5,5'-difluoropentylbenzene, and after stirring at 80 °C for 24 hours, the isolated yield was 95%. The purity was identified by hydrogen spectroscopy as greater than 95%. 1 H NMR (400MHz, CDCl 3 )δ7.64(d,J=8.2Hz,2H),7.61(d,J=7.4Hz,2H),7.53(d,J=8.2Hz,2H),7.47(t,J=7.5Hz,2H) ,7.38(t,J=7.4Hz,1H),7.27(t,J=7.4Hz,2H),7.21-7.11(m,3H),2.61(t,J=7.8Hz,2H),2.26-2.12( m, 2H), 1.73–1.61 (m, 2H), 1.56–1.50 (m, 2H). 19 F NMR (376MHz, CDCl 3)δ-95.1(t,J=16.2Hz,2F). 13 C NMR (125.7MHz, CDCl 3 )δ142.4(t,J=1.4Hz),142.1,140.2,136.3(t,J=26.9Hz),128.8,128.30,128.27,127.7,127.12,127.05,125.7,125.4(t,J=6.1Hz) ,123.1(t,J=242.1Hz...

Embodiment 3

[0114]

[0115] Into a 25mL reaction tube, add 178.2mg (0.9mmol) 3-phenylbenzeneboronic acid, 6.6mg (5mol%, refers to the percentage of moles of 5-bromo-5,5'-difluoropentylbenzene) NiCl 2 · DME, 8 mg (5 mol%) 4,4'-d t Bubpy (4,4'-di-tert-butylbipyridine), 14.6 mg (20 mol%) DMAP, 166 mg (1.2 mmol) K 2 CO 3 , 4 mL of triglyme, injected with 157 mg (0.6 mmol) of 5-bromo-5,5'-difluoropentylbenzene, and after stirring at 80 °C for 24 hours, the isolated yield was 90%. The purity was identified by hydrogen spectroscopy as greater than 95%. 1 H NMR (400MHz, CDCl 3 )δ7.71(s, 1H), 7.67(d, J=7.8Hz, 1H), 7.63(d, J=7.8Hz, 2H), 7.54–7.44(m, 4H), 7.41(t, J=7.3 Hz, 1H), 7.28 (t, J=7.0Hz, 2H), 7.22–7.14 (m, 3H), 2.63 (t, J=7.6Hz, 2H), 2.30–2.14 (m, 2H), 1.74–1.64 (m,2H),1.61–1.51(m,2H). 19 FNMR (376MHz, CDCl 3 )δ-95.4(t,J=16.3Hz,2F). 13 C NMR (125.7MHz, CDCl 3 )δ142.1,141.5,140.5,138.0(t,J=26.8Hz),128.9,128.32,128.29,127.7,127.2,125.8,123.78(t,J=6.2Hz),123.72(t,J=6.3Hz),123.0 (t,...

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Abstract

The invention discloses an aryl or heteroaryl compound substituted with a difluoroalkyl group, a preparation method and an application. The preparation method comprises the following steps: in a solvent, in the presence of a base, a ligand, a catalyst and an additive, the compound shown in formula A and the compound shown in formula B are subjected to the following Suzuki coupling reaction, The compound shown in formula C can be obtained. The preparation method of the present invention has simple and easy-to-obtain raw materials, few reaction steps, high conversion rate and reaction yield, simple operation, cheap and easy-to-obtain catalyst, low cost, good functional group compatibility, wide substrate application range, strong broad-spectrum, and The use of highly toxic reagents is avoided, the safety is high, and the method has good industrial application prospects.

Description

technical field [0001] The present invention relates to a difluoroalkyl-substituted aryl or heteroaryl compound, preparation method and application. Background technique [0002] Difluoroalkyl-substituted aromatic / heteroaromatic compounds have important applications in the fields of medicine, pesticides and materials science. The traditional introduction of difluoromethylene is mainly through deoxyfluorination reagents such as DAST (ie, diethylaminosulfur trifluoride), deoxyfluorination of carbonyl and aldehyde groups, or nucleophilic fluorination in the presence of an oxidant. Thiones or hydrazones are fluorinated by reagents HF-Py, TBABF, etc. However, because the fluorination reagents are often too reactive, the reaction is complicated, and many important functional groups are incompatible, this method is not suitable for synthesizing complex difluoromethylene compounds, thus limiting the application of this method. Although great progress has been made in the introduct...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C25/18C07C25/13C07F7/18C07C47/55C07C69/76C07C255/50C07C255/57C07C43/225C07C49/813C07C49/80C07C211/56C07C317/14C07D209/86C07C33/46C07C69/157C07C317/22C07D211/46C07F17/00C07D277/56C07D209/48C07J51/00C07C271/22C07C69/675C07C17/263C07C45/68C07C67/343C07C253/30C07C41/30C07C209/68C07C29/32C07C315/04C07C269/06
CPCC07C17/263C07C25/13C07C25/18C07C29/32C07C33/46C07C41/30C07C43/225C07C45/68C07C47/55C07C49/80C07C49/813C07C67/343C07C69/157C07C69/675C07C69/76C07C209/68C07C211/56C07C253/30C07C255/50C07C255/57C07C269/06C07C271/22C07C315/04C07C317/14C07C317/22C07D209/48C07D209/86C07D211/46C07D277/56C07F7/1804C07F17/00C07J51/00
Inventor 张新刚肖玉兰闵巧桥
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI