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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
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  • 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

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  • Preparation of 1,3-isoquinoline dione derivative
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  • 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,...

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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

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Application Information

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IPC IPC(8): C07D217/24
CPCC07D217/24
Inventor 夏晓峰祝素丽顾圳
Owner JIANGNAN UNIV
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