CN103980296A - 一种噻唑并吡啶酯类化合物及其制备方法 - Google Patents
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Abstract
本发明涉及一种噻唑并吡啶酯类化合物及其制备方法，该化合物为6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯，制备方法如下：(1)以化合物13，5-二氯-2-氨基吡啶为起始原料，在苯甲酰氯及硫氰酸铵存在下得到苯甲酰基保护的含硫脲的衍生物化合物2；(2)化合物2经过水解得到硫脲衍生物化合物3；(3)化合物3在氢化钠作用下关环生成化合物4；(4)化合物4用亚硝酸异戊酯脱氨基得到目标产物化合物5；(5)化合物5用一氧化碳催化插羰得到目标产物化合物6；所述制备方法是一种原料廉价、合成方法简单的6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯的制备方法，其产物在制备抗炎症的药物方面有着广泛应用前景。
Description
技术领域
本发明涉及中间体化合物生产领域，尤其是一种噻唑并吡啶酯类化合物及其制备方法。
背景技术
根据(Indian Journa l of Chemistry,Section B:Organic C h emistry IncludingMedicinal Chemistry(1980),19B(5),415-17and(1977),15B(2),121-4)and DerPharma Chemica,2012,4(3):1080-1088等文献记载，噻唑并吡啶酯类化合物广泛应用于药物分子中，以该化合物合成的衍生物，在抗炎症以及H3靶点的抑制剂方面具有巨大的临床药物应用价值。可见，由于其良好的药理活性及潜在的药用价值，现阶段噻唑并吡啶酯类化合物的合成倍受关注。
发明内容
本发明所要解决的技术问题在于提供一种噻唑并吡啶酯类化合物。
本发明所要解决的另一技术问题在于提供上述噻唑并吡啶酯类化合物的制备方法。
为解决上述技术问题，本发明的技术方案是：
一种噻唑并吡啶酯类化合物，6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯，其结构式为(Ⅰ)所示，
优选的，上述噻唑并吡啶酯类化合物，所述6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯的核磁共振氢谱数据为1H-NMR(DMSO-d6；400MHZ)4.02(s,3H)8.91(s,1H)8.97(s,1H)。
上述噻唑并吡啶酯类化合物的制备方法，具体步骤如下：
(1)以化合物1(3，5-二氯-2-氨基吡啶)为起始原料，在苯甲酰氯及硫氰酸铵存在下得到苯甲酰基保护的含硫脲的衍生物化合物2；
(2)化合物2经过水解得到硫脲衍生物化合物3；
(3)化合物3在氢化钠作用下关环生成化合物4；
(4)化合物4用亚硝酸异戊酯脱氨基得到化合物5；
(5)化合物5用一氧化碳催化插羰得到目标产物6，其中，
优选的，上述噻唑并吡啶酯类化合物的制备方法，所述化合物5作为中间产物，为新化合物。
上述噻唑并吡啶酯类化合物的制备方法的具体反应方程式如下：
本发明的有益效果是：
上述噻唑并吡啶酯类化合物的制备方法，是一种原料廉价、合成方法简单的6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯的制备方法，其产物6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯在制备抗炎症的药物方面有着广泛应用前景。
附图说明
图1为6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯的HNMR谱图。
具体实施方式
为了使本领域的技术人员更好的理解本发明的技术方案，下面结合具体实施方式对本发明所述技术方案作进一步的详细说明。
实施例1
如图1所示，所述6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯的制备方法，具体步骤如下：
(1)在室温下，将22.7g苯甲酰氯滴入14.9g硫氰酸铵的450ml丙酮溶液(30min滴完)，升温回流，将20g化合物1(3，5-二氯-2-氨基吡啶)投入体系直到原料消失，体系冷却至室温，过滤，滤饼用乙酸乙酯洗涤(50mL*3)至无产品残留，母液旋干，得到粗品(化合物2)50g；TLC信息：原料Rf＝0.6，产品Rf＝0.5。展开剂：石油醚：乙酸乙酯＝3：1。
(2)将50g化合物2溶于250ml甲醇中，室温下，加入250ml4N NaOH的水溶液，回流2h；TLC检测反应完全，旋干甲醇，体系加适量水至溶液变清，温度10℃时用浓盐酸滴入至PH＝9，白色固体析出，过滤并烘干得20.3g粗品(化合物3)，直接用于下一步。TLC信息：原料Rf＝0.5，产品Rf＝0.3。展开剂：石油醚：乙酸乙酯＝3：1，两步收率75.7％。
(3)将11.0g氢化钠(60％)在温度0℃下投入200ml DMF(二甲基甲酰胺)中，20.3g化合物3加入体系回流过夜；TLC检测反应完全，体系冷却至室温，300mL冰水加入体系，用二氯甲烷：异丙醇(3:1)的混合溶剂萃取300mL×3，有机相干燥旋干，柱纯化得纯品(化合物4)8.6g；(二氯甲烷：甲醇＝20:1)。TLC信息：原料Rf＝0.6，产品Rf＝0.2。展开剂：石油醚：乙酸乙酯＝1：1，收率65.0％。
(4)在0℃下，将15.7g亚硝酸异戊酯滴入8.1g化合物4的160ml无水四氢呋喃溶液回流；TLC检测反应应终止，降至室温，滤出不溶物，滤饼用乙酸乙酯(50mL*3)洗涤，旋干体系，柱纯化得3.4g化合物5。(石油醚：乙酸乙酯＝1:1)。TLC信息：原料Rf＝0.3，产品Rf＝0.8。展开剂：二氯甲烷：甲醇＝10：1。收率46.6％。
(5)将0.8g化合物5，0.65g三乙胺(TEA)，0.1g钯催化剂Pd(dppf)Cl2在25ml甲醇中投入高压釜，温度70度，压力1.1MPa，通一氧化碳(CO)
下搅拌6小时；.冷却，TLC检测，原料消失，过滤，滤饼用甲醇洗涤(10mL*3)，滤饼烘干得化合物60.2g，收率27.2％。TLC信息：原料Rf＝0.8，产品Rf＝0.5。展开剂：二氯甲烷：甲醇＝10：1。1H-NMR(DMSO-d6；400MHZ)4.02(s,3H)8.91(s,1H)8.97(s,1H)。
将实施例1所得最终产品6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯(化合物6)作为中间体用于下述合成反应：
所得化合物对人外周血液单核细胞中由LPS诱导的TNF-α释放的抑制作用，实验过程参考申请号为200480005390的发明专利中试验2，测定结果显示，在0.1μM下的抑制可达53.6％。
上述参照具体实施方式对该一种噻唑并吡啶酯类化合物及其制备方法进行的详细描述，是说明性的而不是限定性的，可按照所限定范围列举出若干个实施例，因此在不脱离本发明总体构思下的变化和修改，应属本发明的保护范围之内。
Claims (4)
1.一种噻唑并吡啶酯类化合物，其特征在于：为6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯，其结构式为(Ⅰ)所示，
2.根据权利要求1所述的噻唑并吡啶酯类化合物，其特征在于：所述6-氯-2-噻唑【4，5-b】吡啶甲酸甲酯的核磁共振氢谱数据为
1H-NMR(DMSO-d6；400MHZ)4.02(s,3H)8.91(s,1H)8.97(s,1H)。
3.权利要求1或2所述的噻唑并吡啶酯类化合物的制备方法，其特征在于：具体步骤如下：
(1)以化合物13，5-二氯-2-氨基吡啶为起始原料，在苯甲酰氯及硫氰酸铵存在下得到苯甲酰基保护的含硫脲的衍生物化合物2；
(2)化合物2经过水解得到硫脲衍生物化合物3；
(3)化合物3在氢化钠作用下关环生成化合物4；
(4)化合物4用亚硝酸异戊酯脱氨基得到化合物5；
(5)化合物5用一氧化碳催化插羰得到目标产物化合物6，其中，
4.根据权利要求3所述的噻唑并吡啶酯类化合物的制备方法，其特征在于：所述化合物5作为中间产物，为新化合物。
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104473923A (zh) * | 2014-12-29 | 2015-04-01 | 强红枫 | 一种防治慢性心力衰竭的药物组合物及其应用 |
| CN110590813A (zh) * | 2019-09-05 | 2019-12-20 | 南通大学 | 一种噻唑并[4,5-b]吡啶-6-羧酸及其化学合成方法 |
| CN110818631A (zh) * | 2019-11-08 | 2020-02-21 | 奥锐特药业股份有限公司 | 一种吡啶硫脲衍生物及其制备方法和应用 |
| CN113461635A (zh) * | 2021-07-07 | 2021-10-01 | 上海毕得医药科技股份有限公司 | 4-（2-氯乙基）噻唑-2-羧酸乙酯及其制备方法和应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008129280A1 (en) * | 2007-04-20 | 2008-10-30 | Biolipox Ab | Pyrazoles useful in the treatment of inflammation |
| CN102471334A (zh) * | 2009-08-05 | 2012-05-23 | 莫茨药物股份两合公司 | 促代谢型谷氨酸受体调节剂 |
-
2014
- 2014-05-27 CN CN201410228856.4A patent/CN103980296B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008129280A1 (en) * | 2007-04-20 | 2008-10-30 | Biolipox Ab | Pyrazoles useful in the treatment of inflammation |
| CN102471334A (zh) * | 2009-08-05 | 2012-05-23 | 莫茨药物股份两合公司 | 促代谢型谷氨酸受体调节剂 |
Non-Patent Citations (1)
| Title |
|---|
| SATOSHI KOMORIYA，等: "Design, synthesis, and biological activity of novel factor Xa inhibitors: Improving metabolic stability by S1 and S4 ligand modification", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104473923A (zh) * | 2014-12-29 | 2015-04-01 | 强红枫 | 一种防治慢性心力衰竭的药物组合物及其应用 |
| CN104473923B (zh) * | 2014-12-29 | 2016-08-17 | 巩春智 | 一种防治慢性心力衰竭的药物组合物及其应用 |
| CN110590813A (zh) * | 2019-09-05 | 2019-12-20 | 南通大学 | 一种噻唑并[4,5-b]吡啶-6-羧酸及其化学合成方法 |
| CN110590813B (zh) * | 2019-09-05 | 2021-11-30 | 南通大学 | 一种噻唑并[4,5-b]吡啶-6-羧酸及其化学合成方法 |
| CN110818631A (zh) * | 2019-11-08 | 2020-02-21 | 奥锐特药业股份有限公司 | 一种吡啶硫脲衍生物及其制备方法和应用 |
| CN113461635A (zh) * | 2021-07-07 | 2021-10-01 | 上海毕得医药科技股份有限公司 | 4-（2-氯乙基）噻唑-2-羧酸乙酯及其制备方法和应用 |
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