Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Preparation of 1,3-isoquinoline dione derivative

A technology for isoquinoline dione and derivatives, applied in 1 field, can solve the problem of not many 1,3-isoquinoline dione derivatives, and achieve the effects of simple operation and mild reaction conditions

Active Publication Date: 2015-12-30
JIANGNAN UNIV
View PDF2 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] There are not many reports on the synthesis methods of 1,3-isoquinolinedione derivatives in the literature

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation of 1,3-isoquinoline dione derivative
  • Preparation of 1,3-isoquinoline dione derivative
  • Preparation of 1,3-isoquinoline dione derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1: The preparation method of 2,4-dimethyl-4-(3'-butanone)-1,3-isoquinolinedione, the synthetic route is:

[0022]

[0023] Example 1: The preparation method of 2,4-dimethyl-4-(3'-butanone)-1,3-isoquinolinedione is carried out as follows:

[0024] (1) At room temperature, add N-methyl-N-methacryloylbenzamide (0.203g, 1.0mmol) and methanesulfonic acid (13μL, 0.2mmol) to 6mL of acetone respectively, and add tert Butyl hydroperoxide (500 μL, 3.0 mmol). The mixed system was reacted in an oil bath at 60 to 70°C for 12 hours.

[0025] (2) After the reaction is over, add water to quench. It was extracted twice with ethyl acetate (20 mL×2), washed with saturated brine once, and spin-dried under reduced pressure to remove ethyl acetate. The oily target product (0.145 g, yield 56%) was obtained through column chromatography. 1 HNMR (400MHz): 8.25-8.27 (m, 1H), 7.63-7.68 (m, 1H), 7.42-7.48 (m, 2H), 3.39 (s, 3H), 2.47-2.54 (m, 1H), 2.17- 2.25(m,2H),1.99(s,3H),1.84-1.91(m,1H),1....

Embodiment 2

[0026] Example 2: The preparation method of 4-methyl-2-phenyl-4-(3'-butanone)-1,3-isoquinolinedione, the synthetic route is:

[0027]

[0028] Example 2: The preparation method of 4-methyl-2-phenyl-4-(3'-butanone)-1,3-isoquinolinedione is carried out as follows:

[0029] (1) At room temperature, add N-methacryloyl-N-phenylbenzamide (0.265g, 1.0mmol) and methanesulfonic acid (13μL, 0.2mmol) to 6mL of acetone respectively, and add tert Butyl hydroperoxide (500 μL, 3.0 mmol). The mixed system was reacted in an oil bath at 60 to 70°C for 12 hours.

[0030] (2) After the reaction is over, add water to quench. It was extracted twice with ethyl acetate (20 mL×2), washed with saturated brine once, and spin-dried under reduced pressure to remove ethyl acetate. The target product (0.128 g, yield 40%) was obtained by column chromatography. Melting point: 110-112°C. 1 HNMR (400MHz): 8.26-8.28 (m, 1H), 7.67-7.71 (m, 1H), 7.41-7.50 (m, 5H), 7.17-7.19 (m, 2H), 2.49-2.51 (m, 1H), 2.31-2.37(m,2H...

Embodiment 3

[0031] Example 3: The preparation method of 2,4-dimethyl-4-(3'-pentanone)-1,3-isoquinolinedione, the synthetic route is:

[0032]

[0033] Example 3: The preparation method of 2,4-dimethyl-4-(3'-pentanone)-1,3-isoquinolinedione was carried out as follows:

[0034] (1) At room temperature, add N-methyl N-methacryloyl benzamide (0.203 g, 1.0 mmol) and methanesulfonic acid (13 μL, 0.2 mmol) to 6 mL of 2-butanone, and stir at room temperature Add tert-butyl hydroperoxide (500 μL, 3.0 mmol). The mixed system was reacted for 12 hours in an oil bath at 70 to 80°C.

[0035] (2) After the reaction is over, add water to quench. It was extracted twice with ethyl acetate (20 mL×2), washed with saturated brine once, and spin-dried under reduced pressure to remove ethyl acetate. The oily target product (0.087g, yield 32%) was obtained by column chromatography. 1 HNMR (400MHz): 8.25-8.27 (m, 1H), 7.63-7.67 (m, 1H), 7.42-7.47 (m, 2H), 3.39 (s, 3H), 2.47-2.54 (m, 1H), 2.11 2.30(m,4H),1.81-1.89(m,...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a preparation method of a 1,3-isoquinoline dione derivative. The preparation method is characterized by comprising steps as follows: (1), N-methyl-N-isobutylene acyl benzamide and methane sulfonic acid are added to acetone, 2-butanone or 3-pentanone respectively, TBHP (tert-butyl hydroperoxide) is added while stirring is performed at the room temperature, and a mixed system reacts for 2 hours at certain temperature; (2), after a reaction ends, water is added for quenching, the mixture is extracted with 20 mL of ethyl acetate twice and washed with a saturated salt solution once, and ethyl acetate is removed through spin-drying under reduced pressure; (3), the mixture is subjected to column chromatography, and a target product is obtained.

Description

Technical field [0001] The invention relates to a method for preparing pharmaceutical molecules or intermediates, in particular to a method for preparing 1,3-isoquinolinedione derivatives. Background technique [0002] At present, because people’s demand for complex functional molecules is gradually increasing, 1,3-isoquinolinedione derivatives belong to this type of complex functional molecules. At the same time, 1,3-isoquinolinedione derivatives have Important biological activity, such as HIV-1 integrase inhibitor [BillambozM, SuchaudV, BaillyF, LionC, DemeulemeesterJ, etal.ACSMed.Chem.Lett., 2013, 4:606-611], pancreatic cancer cell anti-tumor activity [BillambozM ,BaillyF,LionC,TouatiN,VezinH,CalmelsC,etal.Med.Chem.,2011,54:1812-1824], cyclin-dependent kinase inhibitors [TsouH,OttengM,TranT,FloydMB,etal.Med.Chem. ,2008,51:3507-3525], caspase inhibitors [ChenYH,ZhangYH,ZhangHJ,LiuDZ,etal.Med.Chem.,2006,49:1613-1623], anti-S180 tumor activity [CN102503888A], etc., therefore Re...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D217/24
CPCC07D217/24
Inventor 夏晓峰祝素丽顾圳
Owner JIANGNAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com