Desloratadine derivative containing gamma-subunit butenolide and synthesizing method thereof

A technology of subunit butenolactone and desloratadine, which is applied in the field of novel desloratadine derivatives and their synthesis, can solve the problems of unseen desloratadine derivatives, and achieve simple and convenient preparation methods with good inhibition role, the effect of broadening the structure type

Inactive Publication Date: 2010-06-16
ZHENGZHOU UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Many Chinese and foreign patents and documents have reported the synthesis of desloratadine, but there are few report

Method used

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  • Desloratadine derivative containing gamma-subunit butenolide and synthesizing method thereof
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preparation example Construction

[0024] The preparation of desloratadine (2): loratadine (1) is placed in 80% ethanol solvent, the potassium hydroxide of 15 times of molar weight is catalyst, nitrogen protection, reflux 8-12 hour until reaction is complete, pump out The ethanol solvent was distilled off, extracted with saturated saline and water, and recrystallized with ethyl acetate to obtain white crystals to obtain desloratadine (2).

[0025] The preparation of compound 6: add 31g desloratadine (2) and 211g of 4-bromomethyl-furan-2-5H-ketone to carbon tetrachloride solution, triethylamine of catalytic amount, stir at room temperature for 6 hours, TLC The reaction was monitored for completion. The reaction mixture was extracted with ethyl acetate, the reaction system was concentrated, and separated by column chromatography to obtain 26 g of pink oil with a yield of 65%, namely compound 6. The experimental data are as follows:

[0026] IR (KBr, cm -1 ): 1776, 1748, 1637, 1589, 1476, 1438, 1142, 1031, 886,...

Embodiment 1

[0027] Embodiment 1: R shown in the preparation general formula II 1 = o-methoxyphenyl, R 2 = Derivatives of H (II-1)

[0028] 406 mg of compound 6 and 204 mg of o-methoxybenzaldehyde were dissolved in 15 mL of methanol, 50 mg of sodium carbonate was added, and reacted at room temperature for 6 hours. After the reaction, add 15 mL of chloroform to dilute, add silica gel to the suction filter funnel and filter to remove the alkali in the system, concentrate the reaction system, and separate by column chromatography to obtain 210 mg of a light yellow solid, which is a single Z-isomer, with a yield of 40%. . The experimental data are as follows:

[0029] m.p=117-119°C.IR(KBr, cm -1 ): 1766, 1598, 1488, 1464, 1438, 1247, 1112, 1024, 826, 756. 1 H NMR (400MHz, CDCl 3, TMS): δ8.41(d, J=4.2Hz, 1H), 8.21(d, J=7.6Hz, 1H), 7.46(d, J=7.4Hz, 1H), 7.31-7.28(m, 1H) , 7.17-7.09(m, 4H), 7.01(m, 1H), 6.92(s, 1H, =C (7″) H), 6.91-6.88(m, 1H), 6.14(s, 1H, =C (3″) H), 3.90(s, 3H, OCH 3 ...

Embodiment 2

[0030] Embodiment 2: R shown in the preparation general formula II 1 = p-Hydroxyphenyl, R 2 = Derivatives of H (II-2)

[0031] Dissolve 406mg of compound 6 and 366mg of p-hydroxybenzaldehyde in 15mL of ethanol, add 50mg of potassium carbonate, and react at room temperature for 24 hours. After the reaction, add 20 mL of chloroform to dilute, add silica gel to the suction filter funnel and filter to remove the alkali in the system, concentrate the reaction system, ethyl acetate crystallizes to obtain 459 mg of a light yellow solid, which is a single Z-isomer, and the yield is 90%. . The experimental data are as follows:

[0032] m.p=198-200℃.IR(KBr, cm -1 ): 1747, 1605, 1573, 1513, 1439, 1371, 1290, 1222, 1166, 928, 827. 1 H NMR (400MHz, CDCl 3 , TMS): δ8.39(d, J=4.6Hz, 1H), 7.66(d, J=8.6Hz, 2H), 7.51(d, J=7.5Hz, 1H), 7.17-7.05(m, 4H) , 6.89(d, J=8.6Hz, 2H), 6.42(s, 1H, =C (7″) H), 6.03(s, 1H, =C (3″) H), 3.48(s, 2H), 3.41-3.37(m, 2H), 2.84-2.76(m, 4H), 2.41-2.38(m, 2H)...

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Abstract

The invention discloses a desloratadine derivative containing gamma-subunit butenolide and a synthesizing method thereof, and belongs to the technical field of organic chemical synthesis. The compounds by using desloratadine as a raw material medicament have the following structural general formula, namely the most synthesized compounds have good inhibiting effect on the shrinkage of histamine-induced isolated ileum smooth muscles of guinea pigs, and the synthesis of the derivative enriches the structural type of anti-histamine medicaments and widens the research fields of the anti-histamine medicaments. The synthesizing method provides a good foundation for the further development and utilization of medicinal molecules, and has important meanings for further developing novel anti-allergic medicaments and developing the medicaments with proprietary intellectual property rights.

Description

technical field [0001] The invention belongs to organic chemical synthesis. It relates to a class of desloratadine derivatives and a synthesis method thereof, in particular to a class of novel desloratadine derivatives containing γ-ylidene butenolactone groups and a synthesis method thereof Background technique [0002] Allergic rhinitis is an allergic disease that affects human health, which can affect the work and quality of life of patients, so it has increasingly attracted global attention. Antihistamines are classified into three classes as the first-line treatment for allergic rhinitis. First-generation antihistamines, such as promethazine and ketotifen, were of limited use due to their sedative and anticholinergic side effects. Second-generation antihistamines, such as cetirizine, loratadine (1), and stin, have significantly fewer CNS and anticholinergic side effects than first-generation antihistamines. Newer generation antihistamines include fexofenadine, levocet...

Claims

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Application Information

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IPC IPC(8): C07D405/14A61P37/08A61P11/02
Inventor 刘宏民刘改芝徐海伟吴亚于德泉
Owner ZHENGZHOU UNIV
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