CN112300093A - 一种磺酰甲脒类化合物及其合成方法和应用 - Google Patents
一种磺酰甲脒类化合物及其合成方法和应用 Download PDFInfo
- Publication number
- CN112300093A CN112300093A CN202011298221.3A CN202011298221A CN112300093A CN 112300093 A CN112300093 A CN 112300093A CN 202011298221 A CN202011298221 A CN 202011298221A CN 112300093 A CN112300093 A CN 112300093A
- Authority
- CN
- China
- Prior art keywords
- sulfonyl
- formamidine compound
- formamidine
- group
- derivatives
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/24—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by sulfur atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
技术领域
本发明涉及化学合成及药物技术领域,具体是一种磺酰甲脒类化合物及其合成方法和应用。
背景技术
磺酰甲脒类化合物广泛地存在于生物活性分子、天然产物和药物中,如:乙溴替丁、法莫替丁、妥伐替丁等药物。同时,它常在制药工业中作为重要的药效团、杂环化合物合成的重要中间体以及作为一种有效的配体参与金属有机反应。因此,对磺酰甲脒类化合物的高效、温和、步骤经济性地合成具有重要的学术意义和工业应用价值。
现已报道的合成方法主要存在三个问题:一、使用存在易爆的有机叠氮试剂作为原料;二、使用腐蚀性强的酸作为催化剂;三、反应的副产物对环境危害性较大。因此,要便捷获取磺酰甲脒类化合物,亟待解决上述挑战性问题。
发明内容
本发明实施例的目的在于提供一种磺酰甲脒类化合物,以解决上述背景技术中提出的问题。
为实现上述目的,本发明实施例提供如下技术方案:
一种磺酰甲脒类化合物,其结构通式为式I:
式中,R1、R2片段为环胺或带有不同取代基的环胺,所述取代基为氟、氯、溴、氰基、氨基、芳基、羟基、羰基、酯基、硝基中的至少一种;R3为苯基及其衍生物、萘基及其衍生物、吡啶及其衍生物、噻吩及其衍生物中的任意一种。
优选的,氨基为叔丁氧羰基保护的氨基;芳基为苯基或被取代的苯基;羟基为叔丁基二甲基硅基或叔丁基二苯基硅基保护的羟基;酯基为羧酸甲酯、乙酯、叔丁酯和苯酯的任意一种。
优选的,R1、R2片段为N-甲基吗啡啉。
优选的,R3为对甲基苯。
优选的,所述磺酰甲脒类化合物的结构为式3a~式3t中的任一种:
本发明实施例的另一目的在于提供一种上述的磺酰甲脒类化合物的合成方法,其包括以下步骤:
将铜催化剂、原料A、原料B和溶剂进行反应后,再经提纯,得到所述磺酰甲脒类化合物;
其中,原料A、原料B的结构通式分别为式A和式B:
上述合成方法的反应路线如下:
优选的,所述铜催化剂为CuCl和/或CuBr。
优选的,所述溶剂为二甲基亚砜、均三甲苯、二甲基甲酰胺和甲苯中的任一种。
本发明实施例的另一目的在于提供一种上述的磺酰甲脒类化合物在在药物后期官能化中的应用。
优选的,所述药物为塞来考昔。
与现有技术相比,本发明实施例的有益效果是:
本发明实施例提供的一种磺酰甲脒类化合物,是通过简单的催化系统,采用简单易得的N-甲基三级胺与磺酰胺一步直接脱氢偶联,制备得到的,无污染,其可应用于药物后期衍生中。
附图说明
图1为实施例1制得的结构式为式3a的磺酰甲脒类化合物的核磁氢谱图;
图2为实施例1制得的结构式为式3a的磺酰甲脒类化合物的核磁碳谱图。
具体实施方式
下面将结合本发明实施例,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。
其中,下述实施例所采用的原料、试剂如下:
CuCl催化剂(国药集团化学试剂有限公司)、CuBr催化剂(Sigma-Aldrich试剂公司)、石油醚(沸程30~60℃,成都市科隆化学品有限公司)、乙酸乙酯(分析纯,重庆川东化工集团有限公司)、均三甲苯(分析纯,阿达玛斯试剂有限公司)、氘代氯仿(CDCl3,氘原子含量99.8%,TMS含量0.03%v/v,瑞士ARMAR公司);核磁管(5mm100/pk 2ST500-8,美国Norell公司)。
所采用的实验仪器如下:
HGZF-II/H-101-3电热恒温鼓风干燥箱(上海跃进医疗器械有限公司)、RCT基本型IKA加热磁力搅拌器(广州艾卡仪器设备有限公司)、EYELA N-1300D-W旋转蒸发仪(东京理化器械株式会社成都分公司)、EL104分析天平(梅特勒-托利多仪器(上海)有限公司)、WFH-204B紫外分析仪(上海勤科分析仪器有限公司)、600MHz核磁共振仪(Bruker ADVANCE III,瑞士Bruker公司)。
实施例1
该实施例提供了一种磺酰甲脒类化合物的合成方法,其反应路线如下:
具体,该合成方法包括以下步骤:
在室温条件下称取CuCl催化剂(4.0g,0.04mmol)、原料A(对甲苯磺酰胺,0.2mmol)、原料B(N-甲基吗啉,0.4mmol)和均三甲苯溶剂(1mL)依次放入密封耐压管中,并在120℃油浴下搅拌24个小时,TLC检测反应,终止反应,得到的反应混合液经过滤,乙酸乙酯洗脱,减压蒸馏除去溶剂,得到粗产品,然后将粗产品进行快速柱层析分离,即可获得结构式为式3a的芳基磺酰甲脒类化合物(其中,原料A和原料B中的R3以及R1、R2片段与式3a对应位置的基团相同):
实施例2
该实施例提供了一种磺酰甲脒类化合物的合成方法,其反应路线如下:
具体,该合成方法包括以下步骤:
在室温条件下称取CuBr催化剂(0.04mmol)、原料A(对甲基苯磺酰胺,0.2mmol)、原料B(N-甲基哌啶,0.4mmol)和二甲基亚砜溶剂(1mL)依次放入密封耐压管中,并在120℃油浴下搅拌24个小时,TLC检测反应,终止反应,得到的反应混合液经过滤,乙酸乙酯洗脱,减压蒸馏除去溶剂,得到粗产品,然后将粗产品进行快速柱层析分离,即可获得结构式为式3b的芳基磺酰甲脒类化合物(其中,原料A和原料B中的R3以及R1、R2片段所指代的基团与式3b对应位置的基团相同):
实施例3
该实施例提供了一种磺酰甲脒类化合物的合成方法,其反应路线如下:
具体,该合成方法包括以下步骤:
在室温条件下称取CuCl催化剂(0.02mmol)、原料A(对甲苯磺酰胺,0.2mmol)、原料B(N-甲基哌啶-4-羧酸甲酯,0.4mmol)和甲苯(1mL)依次放入密封耐压管中,并在120℃油浴下搅拌24个小时,TLC检测反应,终止反应,得到的反应混合液经过滤,乙酸乙酯洗脱,减压蒸馏除去溶剂,得到粗产品,然后将粗产品进行快速柱层析分离,即可获得结构式为式3c的芳基磺酰甲脒类化合物(其中,原料A和原料B中的R3以及R1、R2片段所指代的基团与式3c对应位置的基团相同):
实施例4
该实施例提供了一种磺酰甲脒类化合物的合成方法,其反应路线如下:
具体,该合成方法包括以下步骤:
在室温条件下称取CuCl催化剂(4.0g,0.04mmol)、原料A(对甲基苯磺酰胺,0.2mmol)、原料B(N-甲基哌啶4-(叔丁基二苯基甲硅烷基)氧基),0.4mmol)和二甲基甲酰胺溶剂(1mL)依次放入密封耐压管中并在120℃油浴下搅拌24个小时,TLC检测反应,终止反应,得到的反应混合液经过滤,乙酸乙酯洗脱,减压蒸馏除去溶剂,得到粗产品,然后将粗产品进行快速柱层析分离,即可获得结构式为式3d的芳基磺酰甲脒类化合物(其中,原料A和原料B中的R3以及R1、R2片段所指代的基团与式3d对应位置的基团相同):
实施例5
该实施例提供了一种磺酰甲脒类化合物的合成方法,其反应路线如下:
具体,该合成方法包括以下步骤:
在室温条件下称取CuBr催化剂(0.04mmol)、原料A(对甲苯磺酰胺化合物,0.2mmol)、原料B(N-甲基哌啶-4-((叔丁基二甲基甲硅烷基)氧基)亚甲基),0.4mmol)和均三甲苯溶剂(1mL)依次放入密封耐压管中,并在120℃油浴下搅拌24个小时,TLC检测反应,终止反应,得到的反应混合液经过滤,乙酸乙酯洗脱,减压蒸馏除去溶剂,得到粗产品,然后将粗产品进行快速柱层析分离,即可获得结构式为式3e的芳基磺酰甲脒类化合物(其中,原料A和原料B中的R3以及R1、R2片段所指代的基团与式3e对应位置的基团相同):
需要说明的是,可参照上述实施例1~5的提供的合成方法合成如下结构式的磺酰甲脒类化合物:
此次,上述合成路线可以应用于药物分子(塞来考昔)的衍生,具体合成路线如下:
其中,实施例1制得的结构式为式3a的磺酰甲脒类化合物的核磁氢谱图如附图1所示,实施例1制得的结构式为式3a的磺酰甲脒类化合物的核磁碳谱图如附图2所示。
另外,上述实施例得到的磺酰甲脒类化合物的分析与鉴定表征如下:
1、(E)-4-methyl-N-(morpholinomethylene)benzenesulfonamide(3a):
产率92%;1H NMR(600MHz,Chloroform-d)δ8.20(s,1H),7.77(d,J=6.0Hz,2H),7.27(d,J=12.0Hz,2H),3.77-3.72(m,2H),3.67(s,4H),3.53-3.45(m,2H),2.41(s,3H);13CNM R(150MHz,Chloroform-d)δ157.6,142.7,139.2,129.4,126.6,66.8,65.9,50.3,44.2,21.5.
2、(E)-4-methyl-N-(piperidin-1-ylmethylene)benzenesulfonamide(3b):
产率78%;1H NMR(600MHz,Chloroform-d)δ8.12(s,1H),7.77(d,J=8.3Hz,2H),7.25(s,2H),3.63-3.55(m,2H),3.44-3.37(m,2H),2.40(s,3H),1.69-1.58(m,6H);13C NMR(150MHz,Chloroform-d)δ157.3,142.4,139.7,129.3,126.5,51.9,44.7,26.4,24.9,24.0,21.5.
3、methyl(E)-1-((tosylimino)methyl)piperidine-4-carboxylate(3c):
产率85%;1H NMR(600MHz,Chloroform-d)δ8.14(s,1H),7.76(d,J=8.3Hz,2H),7.26(d,J=12Hz,2H),4.21(dt,J=13.5,4.3Hz,1H),3.71(s,3H),3.68-3.58(m,1H),3.37-3.29(m,1H),3.14-3.06(m,1H),2.67-2.56(m,1H),2.40(s,3H),2.08-2.00(m,1H),2.00-1.93(m,1H),1.84-1.76(m,1H),1.75-1.66(m,1H);13C NMR(150MHz,Chloroform-d)δ173.8,157.4,142.6,139.4,129.4,126.6,52.1,49.9,42.7,40.1,28.3,27.0,21.5.
4、(E)-N-((4-((tert-butyldiphenylsilyl)oxy)piperidin-1-yl)methylene)-4-methylbenzenesulfonamide(3d):
产率67%;1H NMR(600MHz,Chloroform-d)δ8.10(s,1H),7.76(d,J=8.3Hz,2H),7.63(ddd,J=8.1,4.6,1.4Hz,4H),7.46-7.42(m,2H),7.38(ddd,J=9.1,5.6,2.1Hz,4H),7.25(d,J=8.1Hz,2H),4.06(p,J=4.3Hz,1H),3.73(dq,J=13.2,7.1,6.1Hz,2H),3.65(dt,J=13.3,6.7Hz,1H),3.25(dt,J=13.0,4.9Hz,1H),2.39(s,3H),1.64(q,J=4.9Hz,2H),1.59(q,J=5.4,4.9Hz,2H),1.07(s,9H);13C NMR(150MHz,Chlorofor m-d)δ157.17,142.40,139.63,135.64,134.82,133.59,129.96,129.31,127.79,127.73,126.50,66.37,47.13,39.86,33.99,32.54,26.96,21.49,19.22.
5、(E)-N-((4-(((tert-butyldimethylsilyl)oxy)methyl)piperidin-1-yl)methylene)-4-methylbenzenesulfonamide(3e):
产率50%;1H NMR(600MHz,Chloroform-d)δ8.10(s,1H),7.74(d,J=8.3Hz,2H),7.22(s,2H),4.49-4.40(m,1H),3.58(ddt,J=13.1,4.5,2.1Hz,1H),3.42(qd,J=9.9,6.0Hz,2H),3.24(td,J=12.8,3.1Hz,1H),2.75(td,J=13.0,3.2Hz,1H),2.37(s,3H),1.84(d,J=13.1Hz,1H),1.76-1.68(m,2H),1.57(dd,J=34.4,7.1Hz,2H),0.85(s,9H),0.00(s,6H);13C NM R(150MHz,Chloroform-d)δ157.3,142.4,139.7,129.3,126.5,67.0,51.0,43.7,38.5,29.3,27.7,25.9,21.5,18.3,-5.4.
6、N-((E)-((3S,4R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(4-fluorophenyl)piperidin-1-y1)methylene)-4-methylbenzenesulfonamide(3f):
产率32%;(Z:E=1:1)1H NMR(600MHz,Chloroform-d)δ8.30(s,1H),7.88(dd,J=8.3,2.2Hz,2H),7.36(d,J=7.2Hz,2H),7.21-7.16(m,2H),7.10-7.05(m,2H),4.69-4.60(m,1H),3.89-3.71(m,1H),3.50-3.35(m,2H),3.31-3.25(m,1H),3.05-2.71(m,2H),2.52-2.48(m,3H),2.04-1.79(m,3H),0.94(s,9H),0.02--0.04(m,6H);13C NMR(151MHz,Chlorofor m-d)δ161.7(JCF=243Hz),157.4(JCF=7.5Hz),129.35,128.9(JCF=7.5Hz),128.7(JCF=7.5Hz),126.58,126.57,115.67,115.55,115.53,115.41,62.34,61.58,54.11,51.36,46.58,44.81,44.16,43.39,43.05,42.66,34.21,32.82,25.85,25.83,21.51,18.21,18.16,-5.65,-5.70,-5.73.
7、tert-butyl(E)-4-((tosylimino)methyl)piperazine-1-carboxylate(3g):
产率42%;1H NMR(600MHz,Chloroform-d)δ8.20(s,1H),7.77(d,J=8.3Hz,2H),7.27(d,J=6.5Hz,2H),3.62(t,J=5.3Hz,2H),3.53(dd,J=6.5,3.9Hz,2H),3.48-3.41(m,4H),2.41(s,3H),1.47(s,9H);13C NMR(150MHz,Chloroform-d)δ157.7,154.2,142.8,139.1,129.4,126.6,80.9,50.1,43.7,29.7,28.3,21.5,14.1.
产率35%;1H NMR(600MHz,Chloroform-d)δ8.32(s,1H),7.78(d,J=8.3Hz,2H),7.25(d,J=6.0Hz,2H),3.61-3.55(m,2H),3.50-3.44(m,2H),2.40(s,3H),1.98-1.93(m,4H);13C NMR(150MHz,Chloroform-d)δ155.8,142.4,139.7,129.3,126.6,50.0,46.5,25.0,24.4,21.5.
9、(E)-N-(morpholinomethylene)-4-nitrobenzenesulfonamide(3i):
产率32%;1H NMR(600MHz,Chloroform-d)δ8.32(d,J=8.8Hz,2H),8.21(s,1H),8.07(d,J=8.8Hz,2H),3.82-3.76(m,2H),3.71(s,4H),3.56-3.52(m,2H);13C NMR(151MHz,Chloroform-d)δ157.9,149.7,147.7,127.9,124.1,66.8,65.9,50.7,44.5.
10、(E)-4-ethyl-N-(morpholinomethylene)benzenesulfonamide(3j):
产率78%;1H NMR(600MHz,Chloroform-d)δ8.19(s,1H),7.79(d,J=8.3Hz,2H),7.29(d,J=8.4Hz,2H),3.78-3.72(m,2H),3.68(s,4H),3.49(dd,J=5.7,4.1Hz,2H),2.70(q,J=7.6Hz,2H),1.26(t,J=7.6Hz,3H);13C NMR(150MHz,Ch loroform-d)δ157.6,148.9,139.3,128.3,126.7,66.8,66.0,50.3,44.2,28.8,15.2.
11、(E)-2-methyl-N-(morpholinomethylene)benzenesulfonamide(3k):
产率80%;1H NMR(600MHz,Chloroform-d)δ8.19(s,1H),8.01-7.97(m,1H),7.41(td,J=7.5,1.4Hz,1H),7.29(s,2H),3.77-3.74(m,2H),3.70(d,J=1.6Hz,4H),3.52-3.46(m,2H),2.69(s,3H);13C NMR(150MHz,Chloroform-d)δ157.8,140.2,137.5,132.2,132.2,127.6,125.9,66.8,65.9,50.3,44.3,20.6.
11、(E)-N-(morpholinomethylene)benzenesulfonamide(31):
产率73%;1H NMR(600MHz,Chloroform-d)δ8.21(s,1H),7.91-7.87(m,2H),7.55-7.51(m,1H),7.51-7.45(m,2H),3.76(dd,J=5.5,4.3Hz,2H),3.69(s,4H),3.53-3.47(m,2H);13C NMR(150MHz,Chloroform-d)δ157.7,142.0,132.1,128.8,126.6,66.8,65.9,50.4,44.3.
12、(E)-N-(morpholinomethylene)-4-(trifluoromethyl)benzenesulfonamide(3m):
产率63%;1H NMR(600MHz,Chloroform-d)δ8.21(s,1H),8.01(d,J=8.2Hz,2H),7.74(d,J=8.2Hz,2H),3.80-3.75(m,2H),3.70(d,J=1.9Hz,4H),3.55-3.49(m,2H);13CNMR(151MHz,Chloroform-d)δ157.8,145.5,133.7(q,JCF=33.0Hz),127.1,125.96(q,JCF=3.0Hz),123.4(d,JCF=273.3Hz),66.8,65.9,50.5,44.4.
13、(E)-4-fluoro-N-(morpholinomethylene)benzenesulfonamide(3n):
产率65%;1H NMR(600MHz,Chloroform-d)δ8.19(s,1H),7.92-7.86(m,2H),7.18-7.11(m,2H),3.80-3.74(m,2H),3.69(q,J=2.5Hz,4H),3.55-3.47(m,2H);13C NMR(151MHz,Chloroform-d)δ164.8(d,JCF=253.7Hz),157.6,138.17(d,JCF=4.5Hz),129.2(d,JCF=10.6Hz),115.9(d,JCF=22.7Hz),50.42,44.30.
14、(E)-4-(tert-butyl)-N-(morpholinomethylene)benzenesulfonamide(3o):
产率65%;1H NMR(600MHz,Chloroform-d)δ8.20(s,1H),7.83-7.78(m,2H),7.52-7.44(m,2H),3.77-3.73(m,2H),3.69(s,4H),3.52-3.46(m,2H),1.33(s,9H);13C NMR(151MHz,Chloroform-d)δ157.6,155.7,139.0,126.4,125.8,66.8,66.0,50.3,44.2,35.1,31.1.
15、(E)-4-cyano-N-(morpholinomethylene)benzenesulfonamide(3p):
产率90%;1H NMR(600MHz,Chloroform-d)δ8.19(s,1H),8.05-7.94(m,2H),7.82-7.73(m,2H),3.83-3.75(m,2H),3.71(q,J=2.3Hz,4H),3.58-3.44(m,2H);13C NMR(150MHz,Chloroform-d)δ157.8,146.2,132.7,127.3,117.6,115.8,66.8,65.9,50.6,44.5.
16、(E)-N-(morpholinomethylene)thiophene-2-sulfonamide(3q):
产率42%;1H NMR(600MHz,Chloroform-d)δ8.19(s,1H),7.60(dd,J=3.7,1.4Hz,1H),7.52(dd,J=5.0,1.4Hz,1H),7.04(dd,J=5.0,3.7Hz,1H),3.79-3.75(m,2H),3.72(s,4H),3.55-3.49(m,2H);13C NMR(151MHz,Chloroform-d)δ157.7,143.5,131.0,130.9,127.1,66.8,66.0,50.5,44.4.
17、(E)-N-(morpholinomethylene)naphthalene-1-sulfonamide(3r):
产率85%;1H NMR(600MHz,Chloroform-d)δ8.48-8.45(m,1H),8.26(s,1H),7.96-7.84(m,4H),7.60(dddd,J=18.1,8.2,6.9,1.4Hz,2H),3.77-3.74(m,2H),3.68(s,4H),3.53-3.48(m,2H);13C NMR(151MHz,Chloroform-d)δ157.7,138.9,134.6,132.2,129.2,129.1,128.4,127.9,127.3,127.3,122.5,66.8,65.9,50.4,44.3.
18、(E)-4-acetyl-N-(morpholinomethylene)benzenesulfonamide(3s):
产率56%;1H NMR(600MHz,Chloroform-d)δ8.20(s,1H),8.06-8.02(m,2H),8.01-7.96(m,2H),3.81-3.74(m,2H),3.70(s,4H),3.55_3.48(m,2H),2.64(s,3H);13C NMR(151MHz,Chloroform-d)δ197.0,157.8,145.9,139.6,128.7,126.9,66.8,65.9,50.5,44.4,26.9.
19、(E)-N-(morpholinomethylene)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide(3t):
产率38%;1H NMR(600MHz,Chloroform-d)δ8.16(s,1H),7.90-7.83(m,2H),7.44-7.39(m,2H),7.17(d,J=7.9Hz,2H),7.11(d,J=8.2Hz,2H),6.73(s,1H),3.79-3.75(m,2H),3.72-3.66(m,4H),3.54-3.48(m,2H),2.38(s,3H);13C NMR(100MHz,CDCl3,ppm)δ=157.7,145.2,143.9(q,JCF=38.0,77.0Hz),142.0,141.6,139.7,129.7,128.7,127.7,125.7,125.4,121.1(d,JCF=268.0Hz),106.1,66.8,65.9,50.5,44.3,21.4。
以上述依据本发明的理想实施例为启示,通过上述的说明内容,相关工作人员完全可以在不偏离本项发明技术思想的范围内,进行多样的变更以及修改。本项发明的技术性范围并不局限于说明书上的内容,必须要根据权利要求范围来确定其技术性范围。
Claims (10)
2.根据权利要求1所述的一种磺酰甲脒类化合物,其特征在于,氨基为叔丁氧羰基保护的氨基;芳基为苯基或被取代的苯基;羟基为叔丁基二甲基硅基或叔丁基二苯基硅基保护的羟基;酯基为羧酸甲酯、乙酯、叔丁酯和苯酯的任意一种。
3.根据权利要求1所述的一种磺酰甲脒类化合物,其特征在于,R1、R2片段为N-甲基吗啡啉。
4.根据权利要求1所述的一种磺酰甲脒类化合物,其特征在于,R3为对甲基苯。
7.根据权利要求6所述的一种磺酰甲脒类化合物的合成方法,其特征在于,所述铜催化剂为CuCl和/或CuBr。
8.根据权利要求6所述的一种磺酰甲脒类化合物的合成方法,其特征在于,所述溶剂为二甲基亚砜、均三甲苯、二甲基甲酰胺和甲苯中的任一种。
9.一种如权利要求1~5中任一项所述的磺酰甲脒类化合物在在药物后期官能化中的应用。
10.根据权利要求9所述的一种磺酰甲脒类化合物在在药物后期官能化中的应用,其特征在于,所述药物为塞来考昔。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011298221.3A CN112300093B (zh) | 2020-11-18 | 2020-11-18 | 一种磺酰甲脒类化合物及其合成方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011298221.3A CN112300093B (zh) | 2020-11-18 | 2020-11-18 | 一种磺酰甲脒类化合物及其合成方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112300093A true CN112300093A (zh) | 2021-02-02 |
CN112300093B CN112300093B (zh) | 2023-02-24 |
Family
ID=74334919
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011298221.3A Active CN112300093B (zh) | 2020-11-18 | 2020-11-18 | 一种磺酰甲脒类化合物及其合成方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112300093B (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113024423A (zh) * | 2021-03-25 | 2021-06-25 | 山东领海生物科技有限公司 | 一种β-氟,β’-双磺酰亚胺取代酮化合物及其制备方法和应用 |
CN114163401A (zh) * | 2021-12-04 | 2022-03-11 | 商丘师范学院 | 一种n-苯磺酰甲脒化合物的制备方法及应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB538822A (en) * | 1939-12-19 | 1941-08-18 | Geigy Ag J R | Manufacture of amidine derivatives |
-
2020
- 2020-11-18 CN CN202011298221.3A patent/CN112300093B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB538822A (en) * | 1939-12-19 | 1941-08-18 | Geigy Ag J R | Manufacture of amidine derivatives |
Non-Patent Citations (2)
Title |
---|
MARTIN GAZVODA ET AL.: "In Situ Formation of Vilsmeier Reagents Mediated by Oxalyl Chloride: a Tool for the Selective Synthesis of N-Sulfonylformamidines", 《EUR. J. ORG. CHEM.》 * |
QUAN GOU ET AL.: "Copper-Catalyzed Coupling of Sulfonamides with Alkylamines: Synthesis of (E)-N-Sulfonylformamidines", 《J. ORG. CHEM.》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113024423A (zh) * | 2021-03-25 | 2021-06-25 | 山东领海生物科技有限公司 | 一种β-氟,β’-双磺酰亚胺取代酮化合物及其制备方法和应用 |
CN114163401A (zh) * | 2021-12-04 | 2022-03-11 | 商丘师范学院 | 一种n-苯磺酰甲脒化合物的制备方法及应用 |
Also Published As
Publication number | Publication date |
---|---|
CN112300093B (zh) | 2023-02-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN112300093B (zh) | 一种磺酰甲脒类化合物及其合成方法和应用 | |
Aziz et al. | Synthesis of new ß-lactam-N-(thiazol-2-yl) benzene sulfonamide hybrids: Their in vitro antimicrobial and in silico molecular docking studies | |
Ghandi et al. | Pyridine-mediated, one-pot, stereoselective synthesis of acyclic enaminones | |
Han et al. | A convergent route to substituted azetidines and to Boc-protected 4-aminomethylpyrroles | |
Zhang et al. | Facile synthesis of highly functionalized six-membered heterocycles via PPh3-catalyzed [4+ 2] annulations of activated terminal alkynes and hetero-dienes: scope, mechanism, and application | |
CN105669491B (zh) | 一种胺的酰基化方法 | |
Falorni et al. | Synthesis of chiral pyrazoles and isoxazoles as constrained amino acids | |
Jafarpour et al. | Catalytic activity of silica gel in the synthesis of sulfonamides under mild and solvent-free conditions | |
CN111763148A (zh) | 一种含三氟甲基的炔基环戊烯衍生物及其制备方法和应用 | |
Wang et al. | Synthesis and antidiabetic performance of β-amino ketone containing nabumetone moiety | |
Wang et al. | [3+ 2] Cycloaddition reactions of β-diazo-α, α-difluoromethylphosphonates with α, β-unsaturated esters | |
CN106188044A (zh) | 一种碘催化的3‑芳硫基咪唑并[1,5‑a]N‑杂环化合物的合成方法 | |
MX2011002574A (es) | Nuevas orto-aminoanilidas para el tratamiento del cancer. | |
Zhou et al. | Efficient cyclopropanation of aryl/heteroaryl acetates and acetonitriles with vinyl diphenyl sulfonium triflate | |
Brel et al. | Functionalization of bioactive substrates with a F5SCH= CH moiety | |
Ranganath et al. | Design, synthesis and insilico studies of 3-fluoro-3-substituted oxindoles against cancer targets | |
CN107417592A (zh) | 一种1h‑吲哚‑2‑氧代乙酰胺衍生物及其制备方法与应用 | |
CN115819326A (zh) | 一种酰胺类化合物、其制备方法及其应用 | |
Andrews et al. | Phosphine-catalyzed [3+ 2] annulation: Synthesis of ethyl 5-(tert-butyl)-2-phenyl-1-tosyl-3-pyrroline-3-carboxylate | |
CN112898285B (zh) | 含三氟甲基双噁唑类化合物及其合成方法和在抗癌药物中的应用 | |
CN101627008A (zh) | 2-含氟酰基-3-氨基丙烯腈衍生物及其制备方法 | |
Silvestri et al. | Computer-assisted design, synthesis and biological evaluation of novel pyrrolyl heteroaryl sulfones targeted at HIV-1 reverse transcriptase as non-nucleoside inhibitors | |
Qureshi et al. | Tertiary‐Amine Controlled (3+ 3) or (4+ 2) Annulations of β′‐Acetoxy Allenoates with N‐Sulfonyl Ketimines: An Entry to m‐Teraryl and Fused Dihydropyridines | |
CN105622544B (zh) | 一种n-磺酰基-3,4-二氢-2h-1,4-噻嗪的合成方法 | |
CN106831474A (zh) | 一种含α‑芳基‑α,β‑二氨基酸酯衍生物及其合成方法和应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |