Chromodihydropyran sulfonamide spiro compound and preparation method thereof

A technology of chroman-like sulfonamide spiro and chroman, which is applied in the field of chroman-like sulfonamide spiro compounds and their preparation, and can solve the problem of undiscovered sulfonamide spiro compounds, etc. problem, to achieve the effect of increasing diversity and improving polarity

Active Publication Date: 2015-09-23
SHANGHAI STA PHARMA R&D CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no research report on the special synthesis of sulfonamide spiro compounds in the literature

Method used

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  • Chromodihydropyran sulfonamide spiro compound and preparation method thereof
  • Chromodihydropyran sulfonamide spiro compound and preparation method thereof
  • Chromodihydropyran sulfonamide spiro compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: 6-bromo-2,2-dimethylspiro[chroman-4-3'-(1,2,5)thiodiazoline]-4'-one-S, Preparation of S-dioxide I-a

[0043]

[0044] Steps:

[0045] 1-(5-bromo-2-hydroxyphenyl)ethanone 1 (570 g, 2.6 mol) was dissolved in 970 ml of acetone (13 mol) and 5.5 liters of toluene in a mixed solution, and then 220 ml of tetrahydro Pyrrole (2.6 mol), stirred at 80°C for 16 hours. The reaction mixture was concentrated into a black oily crude product, which was purified by column chromatography to obtain 544 g of light yellow oily 6-bromo-2,2-dimethylchroman-4-one 2 with a yield of 80%. HNMR (CDCl 3 ) d: 7.84 (s, 1H), 7.42 (d, J = 8.8 Hz, 1H), 6.73 (d, J = 8.8 Hz, 1H), 2.61 (s, 2H), 1.32 (s, 6H).

[0046] 200 g of 6-bromo-2,2-dimethylchroman-4-one 2 (0.78 mol), 550 g of ammonium carbonate (5.5 mol), 104 g of potassium cyanide (1.56 mol) and 1.2 Add ammonium formate into the autoclave. The mixture was stirred at 100°C for 48 hours, then cooled to room temperature and dilut...

Embodiment 2

[0056] Example 2: 6-bromo-2,2,5'-trimethylspiro[chroman-4-3'-(1,2,5)thiodiazoline]-4'-one Preparation of -S,S-dioxide I-b

[0057]

[0058] Steps:

[0059] 359 mg of 6-bromo-2,2-dimethylspiro[chroman-4-3'-(1,2,5)thiodiazoline]-4'-one-S,S - Dioxide I-a (1 mmol), added to a solution in 50 ml of tetrahydrofuran, followed by 60 mg of sodium hydride (60% in mineral oil). The mixture was stirred at room temperature 25°C for 0.5 hours, and then 142 mg of methyl iodide was added to the mixture. The reaction solution was stirred at room temperature for 16 hours and then concentrated. The resulting crude product was separated by column chromatography to obtain 340 mg of 6-bromo-2,2,5 '-Trimethylspiro[chroman-4-3'-(1,2,5)thiodiazoline]-4'-one-S,S-dioxide I-b. Yield: 91%.

[0060] HNMR (DMSO) d: 11.2 (br s, 1H), 7.35 (s, 1H), 7.22 (d, J = 8.8 Hz, 1H), 6.95 (br s, 1H), 6.65 (d, J = 8.8 Hz, 1H), 2.71 (s, 3H), 2.41 (d, J = 14.4 Hz, 1H), 1.88 (d, J = 14.4 Hz, 1H), 1.34 (s, 3H),...

Embodiment 3

[0061] Example 3: 6-bromo-2,2-dimethyl-5'-benzylspiro[chroman-4-3'-(1,2,5)thiodiazoline]-4 Preparation of '-keto-S,S-dioxide 1-c

[0062]

[0063] Steps:

[0064] 359 mg of 6-bromo-2,2-dimethylspiro[chroman-4-3'-(1,2,5)thiodiazoline]-4'-one-S,S - Dioxide I-a (1 mmol), added to a solution in 50 ml of tetrahydrofuran, followed by 60 mg of sodium hydride (60% in mineral oil). The mixture was stirred at room temperature 25°C for 0.5 hours, then 126 mg of benzyl chloride was added to the mixture, the reaction solution was stirred at room temperature for 16 hours and then concentrated. The resulting crude product was separated by column chromatography to obtain 420 mg of 6-bromo-2,2-di Methyl-5'-benzylspiro[chroman-4-3'-(1,2,5)thiodiazoline]-4'-one-S,S-dioxide 1- c. Yield: 93%.

[0065] HNMR (DMSO) d: 7.35 (s, 1H), 7.33-7.29 (m, 3H), 7.22 (d, J = 8.8 Hz, 1H), 7.19 (d, J = 7.6 Hz, 2H), 6.95 (br s, 1 H), 6.65 (d, J = 8.8 Hz, 1H), 4.50 (s, 2H), 2.41 (d, J = 14.4 Hz, 1H)...

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Abstract

The invention relates to a benzo dihydropyran sulfamide spiro-compound and a preparation method thereof, and mainly solves the technical problems that the synthesis method of the benzo dihydropyran sulfamide spiro-compound has not been reported in any literature and the medical structure-activity relationship thereof can not be screened in the prior art. The structural general formula is shown in the specification, wherein R1 and R2 are hydrogen, halogen, alkyl or aryl; and preferably, alkyl or aryl is one of C1-C4 straight-chain alkyl, alkyl containing substituent branch chains and substituent aryl.

Description

technical field [0001] The invention relates to a chroman sulfonamide spiro compound and a preparation method thereof. Background technique [0002] As early as the 1970s, spirocyclic compounds were found to have biological activity. After more than 30 years of research and development, a variety of spirocyclic derivatives have been proven to have promising therapeutic effects, such as anti-depression, inhibition of angiogenesis (anti-tumor), anti-platelet aggregation (anti-thrombosis), and anti-alheian Merz disease (senile dementia), etc. The structure of the sulfonamide spiro compound contains both hydrogen bond acceptors and donors (R 2 = H). The simultaneous presence of hydrogen bond acceptors and donors can increase the chance of interaction between the substrate and the target, and thus may increase the degree of binding between the substrate and the protein target to increase the activity of the substrate. It has been widely proven that it has various Such biologi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D513/10A61P1/00
Inventor 肖贻崧张培权李联华柏祝贺海鹰陈曙辉
Owner SHANGHAI STA PHARMA R&D CO LTD
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