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CN104892581A - 具有杀菌活性的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物、其制备方法及应用 - Google Patents

具有杀菌活性的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物、其制备方法及应用 Download PDF

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CN104892581A
CN104892581A CN201410082965.XA CN201410082965A CN104892581A CN 104892581 A CN104892581 A CN 104892581A CN 201410082965 A CN201410082965 A CN 201410082965A CN 104892581 A CN104892581 A CN 104892581A
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CN104892581B (zh
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贺红武
王威
贺军波
张�林
朱国中
郭新娟
邹鹏
谭效松
彭浩
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Central China Normal University
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Abstract

本发明公开了一种具有杀菌活性的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物、其制备方法及应用，结构式其中，R1表示氢或I；X表示O、NH或S；Y表示苯甲酰胺硫羰基或取代苯甲酰胺硫羰基、2-苯基-1,3,4-噻（噁）二唑-5-基或2-取代苯基-1,3,4-噻（噁）-5-基、苯甲（乙酮）亚胺基或取代苯甲（乙酮）亚胺基；在Y所涉及的苯环上的取代基主要为：H、卤素、硝基、氰基、CF3、C1-4烷基、甲氧基、C1-2羧酸基或羧酸酯基。本发明化合物对小麦赤霉病菌、水稻纹枯病菌、黄瓜灰霉病菌、番茄早疫病菌、烟草赤星病菌和黄瓜炭疽病菌具有显著防效，可用作杀菌活性成分。

Description

具有杀菌活性的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物、其制备方法及应用
技术领域
本发明涉及2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物、其制备方法及其应用。
背景技术
丙酮酸脱氢酶系是生物体内能量代谢调控过程中的一类重要酶系，它连接着糖酵解得到的丙酮酸转化为三羧酸循环的底物乙酰辅酶A的过程。基于其重要的生化特点，丙酮酸脱氢酶系完全可作为农药靶标进行研究。近年来，本发明人以微生物中丙酮酸脱氢酶系为靶标，设计合成了具有作为杀菌剂应用价值的新型结构化合物。例如，A类（贺红武等，中国发明专利，申请号为201110268908.7）化合物则显示了优异的杀菌活性。
发明内容
本发明的目的在于探索具有杀菌活性的新型化合物，并提供了一种具有杀菌活性的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物、其制备方法及应用。
本发明在A类化合物基础上进一步优化了Y的结构类型，提出了一种具有杀菌活性的新型化合物，其具有通式（I）的结构：
其中，R1表示氢或I；X表示O、NH或S；Y表示苯甲酰胺硫羰基或取代苯甲酰胺硫羰基、2-苯基-1,3,4-噻（噁）二唑-5-基或2-取代苯基-1,3,4-噻（噁）-5-基、苯甲（乙酮）亚胺基或取代苯甲（乙酮）亚胺基；在Y所涉及的苯环上的取代基主要为：H、卤素、硝基、氰基、CF3、C1-4烷基、甲氧基、C1-2羧酸基或羧酸酯基；取代基在苯环任意位置上的单取代或多取代，取代基相同或不同。
化合物（I）包括以通式（I-1）表示的[1-（2-甲基-4-氨基嘧啶-5-甲基）-1H-1,2,3-三唑]-4-甲基-（取代苯甲酰基）硫代氨基甲酸酯（硫脲）化合物、以通式（I-2）表示的N-（（1-（（2-甲基-4-氨基嘧啶-5-基）甲基）-1H-1,2,3-三唑-4-基）甲基）-2-取代苯基-1,3,4-噻（噁）-5-基硫醚化合物、以通式（I-3）表示的O-[1-（2-甲基-4-氨基嘧啶-5-甲基）-1H-1,2,3-三唑-4-基]取代苯甲（乙酮）肟醚化合物。
本发明所提出的通式（I-1）、通式（I-2）、通式（I-3）的化合物结构均未见报道，通式（I-1）、通式（I-2）、通式（I-3）的结构分别定义如下：
通式（I-1）中，X为氧或NH；R1的定义与通式（I）的R1定义相同；R2为：H、卤素、硝基、甲氧基或C1-4烷基；R3为：H、卤素、硝基、氰基、CF3、C1-4烷基或甲氧基；R2与R3位置可互换。
通式（I-2）中，X为氧或S；R1的定义与通式（I）的R1定义相同；R2为：H、卤素、硝基或C1-4烷基；R3为：H、卤素、硝基、CF3、甲氧基或C1-4烷基；R2与R3位置可互换。
通式（I-3）中，R1的定义与通式（I）的R1定义相同；R2为H、硝基或卤素；R3为：H、卤素、硝基、C1-4烷基或甲氧基；R2与R3位置可换；R4为H或甲基。
本发明具有通式（I）结构的化合物对小麦赤霉病菌、水稻纹枯病菌、黄瓜灰霉病菌、番茄早疫病菌、烟草赤星病菌和黄瓜炭疽病菌具有显著的防效，可用作杀菌剂的活性成分。
具有通式（I-1）结构的化合物的制备方法，是在催化剂和有机碱或仅在催化剂的存在下，使化合物（II）与炔中间体（III）在-10～80℃温度下反应12-24小时关环生成，A法。反应式如下：
上述反应式（1）中，通式（III）中R1、R2、R3、X的定义与通式（I-1）中R1、R2、R3、X的定义相同。
上述A法反应中，化合物（II）、中间体（III）、催化剂和有机碱的摩尔比为1：（0.8-1.2）：（0.01-0.15）：2；反应溶剂采用有机溶剂：二氯甲烷、二氧六环、二氯乙烷、丙酮、叔丁醇、水、苯、乙酸乙酯、四氢呋喃、乙腈、N,N-二甲基甲酰胺或二甲基亚砜；催化剂为：CuI、CuBr(PPh3)3、CuSO4·5H2O:抗坏血酸钠、CuBr或Cu(OAc)2；有机碱为：三乙胺、二异丙基乙基胺、吡啶或六氢吡啶。
具有通式（I-2）结构的化合物的制备方法，是在催化剂和有机碱或仅在催化剂的存在下，使化合物（II）与中间体（IV）在-10～80℃温度下反应12-24小时关环生成，B法。反应式如下：
上述反应式（2）中，通式（IV）中R1、R2、R3、X的定义与通式（I-2）中R1、R2、R3、X的定义相同。
上述B法反应中，化合物（II）、中间体（IV）、催化剂和有机碱的摩尔比为1：（0.8-1.2）：（0.01-0.15）：2；反应溶剂采用有机溶剂：二氯甲烷、二氧六环、二氯乙烷、丙酮、叔丁醇：水、苯、乙酸乙酯、四氢呋喃、乙腈、N,N-二甲基甲酰胺或二甲基亚砜；催化剂为：CuI、CuBr(PPh3)3、CuSO4·5H2O:抗坏血酸钠、CuBr或者Cu(OAc)2；有机碱为：三乙胺、二异丙基乙基胺、吡啶或六氢吡啶。
具有通式（I-2）结构的化合物的制备方法，是在催化剂和有机碱或仅在催化剂的存在下，使化合物（II）与中间体（V）在-10～80℃温度下反应12-24小时关环生成，C法。反应式如下：
上述反应式（3）中，通式（V）中R1、R2、R3、R4的定义与通式（I-3）中R1、R2、R3、R4的定义相同。
上述C法反应中，化合物（II）、中间体（V）、催化剂和有机碱的摩尔比为1：（0.8-1.2）：（0.01-0.15）：2；反应溶剂采用有机溶剂：二氯甲烷、二氧六环、二氯乙烷、丙酮、叔丁醇：水、苯、乙酸乙酯、四氢呋喃、乙腈、N,N-二甲基甲酰胺或二甲基亚砜；催化剂为：CuI、CuBr(PPh3)3、CuSO4·5H2O:抗坏血酸钠、CuBr或者Cu(OAc)2；有机碱为：三乙胺、二异丙基乙基胺、吡啶或六氢吡啶。
具体实施方式
下面通过实施例具体地说明本发明化合物（I），包括化合物（I-1）、（I-2）、（I-3）的制备方法，这些实施例仅对本发明进行说明，而不是对本发明进行限制。
下述实施例中采用的化合物（II）可参见文献1中记载的方法进行制备。
实施例1：中间体III-1的制备
在装有干燥管、低温温度计、恒压滴液漏斗的100mL三颈瓶中加入0.28g炔丙醇（5mmol）、0.5g三乙胺（5mmol）和10mL乙腈，在低温恒温反应浴中冷却至4℃，缓慢加入10mL的苯甲酰异硫氰酸酯的乙腈溶液，其中苯甲酰异硫氰酸酯为5mmol；维持反应液温度低于5℃，待苯甲酰异硫氰酸酯的乙腈溶液滴加完毕后，转移至室温反应，TLC（薄层色谱）监测。反应结束后，依次用5%稀盐酸、饱和碳酸氢钠溶液及饱和食盐水洗涤至溶液呈中性。然后用二氯甲烷（15mL×3次）萃取水相，经合并有机相、无水硫酸钠干燥过夜、抽滤、滤液浓缩即得粗产品，经硅胶柱层析梯度淋洗（石油醚：乙酸乙酯=3:1）即得纯品。
R1、R2、R3、X为其他取代基的中间体III按中间体III-1类似方法制得。
实施例2：中间体IV-1的制备
于50mL圆底烧瓶中加入4.0mmol的5-苯基-1,3,4-噻二唑-2-硫醇、4.0mmol碳酸钾粉末，溶于15mL干燥二甲基亚砜，室温下滴加入4.8mmol溴丙醇，于室温下搅拌反应，TLC（薄层色谱）监测反应至原料点消失，停止反应后，将体系倾入100mL水中，充分搅拌，有大量固体析出，抽滤得粗品IV-1，无需提纯。
R1、R2、R3、X为其他取代基的中间体IV按中间体IV-1类似方法制得。
实施例3：中间体V-1的制备
分别将5mmol苯甲醛肟、5mmol溴丙炔溶于20mL无水乙腈，然后加入5mmol氢氧化钠，回流反应8小时，TLC（薄层色谱）监测反应完全。减压除去乙腈，然后依次经稀盐酸、饱和碳酸氢钠溶液、饱和食盐水洗涤，用乙酸乙酯（20mL×3次）萃取水相，经合并有机相、无水硫酸钠干燥，浓缩得粗产品，丙酮重结晶得中间体V-1。
R1、R2、R3、R4为其他取代基的中间体V按中间体V-1类似方法制得。
实施例4：化合物1的制备
将1mmol2-甲基-4-氨基-5-叠氮甲基嘧啶和1mmol O-丙炔基苯甲酰基氨基硫代甲酸酯溶于20mL四氢呋喃中，加入2mmol三乙胺和0.1mmol碘化亚铜CuI，在60-70℃搅拌反应10-15小时，TLC（薄层色谱）监测反应至完全，加水有固体析出，经减压过滤、水洗、烘干的粗品。用N,N-二甲基甲酰胺和水重结晶，得黄色固体状的目标化合物，产率88%，mp：120-122℃。
元素分析/%：计算值：C,53.25;H,4.47;N,25.57;S,8.36;实测值：C,53.09;H,4.74;N,25.33;S,8.04;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.35(s,2H,CH2),5.44(s,2H,CH2),5.66(s,2H,NH2),7.41-8.03(m,5H,Ar-H),7.72(s,1H,CH),8.19(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ25.2,46.9,57.9,108.2,125.0,128.8,129.2,133.5,142.0,156.4,161.6,165.5,167.2,179.3.IR(KBr):1277(C=S),1702(C=O),3150(N-H),3512cm-1.ESI-MS(m/z):384(M++1).
化合物2-20按化合物1类似方法制得，结构鉴定数据如下：
化合物2
所得纯品为黄色固体，产率87%，m.p.115-116℃;。元素分析/%：计算值：C,48.86;H,3.86;N,23.46;S,7.67;实测值：C,48.83;H,4.20;N,23.57;S,7.82;1H NMR(400MHz,CDCl3):δ2.50(s,3H,CH3),5.36(s,2H,CH2),5.45(s,2H,CH2),5.58(s,2H,NH2),7.28-7.85(m,4H,Ar-H),7.46(s,1H,CH),8.19(s,1H,CH).IR(KBr):1265(C=S),1717(C=O),3145(N-H),3544cm-1.ESI-MS(m/z):418(M++1).
化合物3
所得纯品为黄色固体，产率84%，m.p.139-141℃。元素分析/%：计算值：C,48.86;H,3.86;N,23.46;S,7.67;实测值：C,49.24;H,3.96;N,23.53;S,7.74;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.38(s,2H,CH2),5.44(s,2H,CH2),5.66(s,2H,NH2),7.35-7.99(m,4H,Ar-H),7.72(s,1H,CH),8.05(s,1H,CH).IR(KBr):1270(C=S),1722(C=O),3147(N-H),3454cm-1.ESI-MS(m/z):418(M++1).
化合物4
所得纯品为黄色固体，产率78%，m.p.124-125℃。元素分析/%：计算值：C,48.86;H,3.86;N,23.46;S,7.67;实测值：C,49.02;H,4.05;N,23.33;S,7.75;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.36(s,2H,CH2),5.43(s,2H,CH2),5.63(s,2H,NH2),7.39-7.97(m,4H,Ar-H),7.71(s,1H,CH),8.20(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ25.2,46.8,58.1,108.2,125.0,128.1,131.0,138.4,141.7,156.3,161.5,164.6,167.6,180.3.IR(KBr):1277(C=S),1708(C=O),3110(N-H),3452cm-1.ESI-MS(m/z):418(M++1).
化合物5
所得纯品为浅黄色固体，产率73%，m.p.156-157℃。元素分析/%：计算值：C,54.39;H,4.82;N,24.67;S,8.07;实测值：C,54.69;H,4.99;N,24.65;S,7.62;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),2.62(s,3H,CH3),5.36(s,2H,CH2),5.41(s,2H,CH2),5.67(s,2H,NH2),7.22-7.96(m,4H,Ar-H),7.71(s,1H,CH),8.20(s,1H,CH).IR(KBr):1270(C=S),1702(C=O),3150(N-H),3512cm-1.ESI-MS(m/z):398(M++1).
化合物6
所得纯品为黄色固体，产率83%，m.p.123-125℃。元素分析/%：计算值：C,54.39;H,4.82;N,24.67;S,8.07;实测值：C,54.17;H,4.73;N,23.55;S,8.01;1H NMR(400MHz,CDCl3):δ2.51(s,3H,CH3),2.65(s,3H,CH3),5.38(s,2H,CH2),5.43(s,2H,CH2),5.54(s,2H,NH2),7.32-7.93(m,4H,Ar-H),7.71(s,1H,CH),8.08(s,1H,CH).IR(KBr):1253(C=S),1709(C=O),3118(N-H),3452cm-1.ESI-MS(m/z):398(M++1).
化合物7
所得纯品为浅黄色固体，产率71%，m.p.146-148℃。元素分析/%：计算值：C,50.87;H,4.02;N,24.43;S,7.99;实测值：C,51.04;H,4.29;N,24.32;S,7.66;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.36(s,2H,CH2),5.46(s,2H,CH2),5.60(s,2H,NH2),7.11-7.93(m,4H,Ar-H),7.52(s,1H,CH),8.20(s,1H,CH).IR(KBr):1253(C=S),1729(C=O),3148(N-H),3453cm-1.ESI-MS(m/z):402(M++1).
化合物8
所得纯品为黄色固体，产率76%，m.p.132-133℃。元素分析/%：计算值：C,50.87;H,4.02;N,24.43;S,7.99;实测值：C,50.92;H,4.34;N,24.40;S,7.80;1H NMR(400MHz,CDCl3):δ2.50(s,3H,CH3),5.36(s,2H,CH2),5.43(s,2H,CH2),5.62(s,2H,NH2),7.07-8.06(m,4H,Ar-H),7.71(s,1H,CH),8.20(s,1H,CH).IR(KBr):1253(C=S),1721(C=O),3111(N-H),3454cm-1.ESI-MS(m/z):402(M++1).
化合物9
所得纯品为黄色固体，产率70%，m.p.134-136℃。元素分析/%：计算值：C,44.16;H,3.49;N,21.21;S,6.94;实测值：C,44.44;H,3.77;N,31.38;S,6.84;1H NMR(400MHz,CDCl3):δ2.50(s,3H,CH3),5.36(s,2H,CH2),5.45(s,2H,CH2),5.61(s,2H,NH2),7.33-7.80(m,4H,Ar-H),7.66(s,1H,CH),8.20(s,1H,CH).IR(KBr):1270(C=S),1721(C=O),3145(N-H),3453cm-1.ESI-MS(m/z):463(M++1).
化合物10
所得纯品为黄色固体，产率77%，m.p.141-142℃。元素分析/%：计算值：C,48.68;H,3.60;N,23.38;S,7.65;实测值：C,48.32;H,3.86;N,23.62;S,7.54;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.36(s,2H,CH2),5.42(s,2H,CH2),5.59(s,2H,NH2),6.92-7.71(m,4H,Ar-H),7.71(s,1H,CH),8.20(s,1H,CH).IR(KBr):1265(C=S),1725(C=O),3139(N-H),3440cm-1.ESI-MS(m/z):420(M++1).
化合物11
所得纯品为黄色固体，产率50%，m.p.73-75℃。素分析/%：计算值：C,44.11;H,3.27;N,24.21;S,6.93;实测值：C,44.25;H,3.42;N,24.22;S,6.82;1H NMR(600MHz,DMSO-d6):δ2.29(s,3H,CH3),5.44(s,2H,CH2),5.49(s,2H,CH2),6.98(s,2H,NH2),7.99-8.27(m,3H,Ar-H),8.38(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ25.3,46.8,109.3,122.4,125.2,125.5,132.0,132.6,135.4,141.1,142.9,149.4,156.2,161.4,163.5,194.5.IR(KBr):1243(C=S),1603(C=O),3369(N-H)cm-1.EI-MS(m/z,%):462(M+,2).
化合物12
所得纯品为黄色固体，产率56%，m.p.62-64℃。元素分析/%：计算值：C,45.14;H,3.34;N,21.68;S,7.09;实测值：C,45.25;H,3.56;N,21.95;S,7.25;1H NMR(600MHz,DMSO-d6):δ2.30(s,3H,CH3),5.38(s,2H,CH2),5.47(s,2H,CH2),6.98(s,2H,NH2),7.53-7.81(m,3H,Ar-H),8.25(s,1H,CH).IR(KBr):1245(C=S),1604(C=O),3366(N-H)cm-1.EI-MS(m/z,%):451(M+,2).
化合物13
所得纯品为黄色固体，产率87%，m.p.96-98℃。元素分析/%：计算值：C,51.46;H,4.77;N,22.11;S,7.23;实测值：C,51.62;H,4.59;N,22.95;S,6.98;1H NMR(400MHz,DMSO-d6):δ2.30(s,3H,CH3),3.78(s,3H,OCH3),3.81(s,3H,OCH3),5.34(s,2H,CH2),5.45(s,2H,CH2),6.94(s,2H,NH2),7.05(d,1H,J=8.8Hz,Ar-H),7.41(s,1H,Ar-H),7.56(d,1H,J=7.2Hz,Ar-H),8.22(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ25.3,46.7,55.5,55.7,57.6,111.0,111.6,121.4,123.3,124.9,142.2,148.4,153.1156.0,160.9,161.4,165.2,166.9,180.3.IR(KBr):1271(C=S),1706(C=O),3365(N-H)cm-1.EI-MS(m/z,%):462(M+,2).
化合物14
所得纯品为黄色固体，产率44%，m.p.>260℃。元素分析/%：计算值：C,43.13;H,3.19;N,26.63;S,6.77;实测值：C,43.35;H,3.42;N,26.12;S,6.53;1H NMR(600MHz,DMSO-d6):δ2.29(s,3H,CH3),5.50(s,2H,CH2),5.52(s,2H,CH2),7.00(s,2H,NH2),8.30(s,1H,CH),8.87(s,1H,Ar-H),9.03(s,1H,Ar-H).IR(KBr):1277(C=S),1726(C=O),3362(N-H)cm-1.EI-MS(m/z,%):473(M+,4).
化合物15
所得纯品为黄色固体，产率34%，m.p.206-208℃。元素分析/%：计算值：C,51.46;H,4.77;N,22.11;S,7.23;实测值：C,51.27;H,4.49;N,22.22;S,7.38;1H NMR(400MHz,DMSO-d6):δ2.29(s,3H,CH3),3.78(s,3H,OCH3),3.81(s,3H,OCH3),5.34(s,2H,CH2),5.48(s,2H,CH2),6.98(s,2H,NH2),7.04(d,1H,J=8.4Hz,Ar-H),7.41(d,1H,J=1.8Hz,Ar-H),7.56(d,1H,J=8.4Hz,Ar-H).IR(KBr):1271(C=S),1706(C=O),3369(N-H)cm-1.EI-MS(m/z,%):443(M+,4).
化合物16
所得纯品为黄色固体，产率77%，m.p.141-142℃。元素分析/%：计算值：C,48.68;H,3.60;N,23.38;S,7.65;实测值：C,48.32;H,3.86;N,23.62;S,7.54;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.36(s,2H,CH2),5.42(s,2H,CH2),5.59(s,2H,NH2),6.92-7.71(m,4H,Ar-H),7.71(s,1H,CH),8.20(s,1H,CH).IR(KBr):1265(C=S),1725(C=O),3139(N-H),3440cm-1.EI-MS(m/z,%):420(M++1,100).
化合物17
所得纯品为黄色固体，产率33%，m.p.230-232℃。元素分析/%：计算值：C,45.14;H,3.34;N,21.68;S,7.09;实测值：C,45.22;H,3.11;N,21.88;S,7.20;1H NMR(400MHz,DMSO-d6):δ2.32(s,3H,CH3),5.39(s,2H,CH2),5.51(s,2H,CH2),7.06(s,2H,NH2),7.53-7.81(m,3H,Ar-H),8.25(s,1H,CH).IR(KBr):1271(C=S),1712(C=O),3426(N-H)cm-1.EI-MS(m/z,%):451(M+,2).
化合物18
所得纯品为黄色固体，产率30%，m.p.191-193℃。元素分析/%：计算值：C,40.09;H,3.17;N,19.25;S,6.30;实测值：C,40.20;H,3.45;N,19.18;S,6.16;1H NMR(600MHz,DMSO-d6):δ2.29(s,3H,CH3),4.49(s,2H,CH2),5.43(s,2H,CH2),6.97(s,2H,NH2),7.16-7.85(m,3H,Ar-H),7.97(s,1H,CH).IR(KBr):1285(C=S),1715(C=O),3364(N-H)cm-1.EI-MS(m/z,%):509(M+,2).
化合物19
所得纯品为黄色固体，产率40%，m.p.138-140℃。元素分析/%：计算值：C,47.89;H,3.57;N,21.72;S,7.10;实测值：C,47.05;H,3.64;N,21.67;S,7.38;1H NMR(600MHz,DMSO-d6):δ2.30(s,3H,CH3),5.25(s,2H,CH2),5.45(s,2H,CH2),6.95(s,2H,NH2),7.49-7.79(m,4H,Ar-H),8.01(s,1H,CH),8.03(s,1H,CH).IR(KBr):1323(C=S),1656(C=O),3376(N-H)cm-1.EI-MS(m/z,%):451(M+,2).
化合物20
所得纯品为黄色固体，产率37%，m.p.>260℃。元素分析/%：计算值：C,52.93;H,3.95;N,27.43;S,7.85;实测值：C,52.78;H,3.72;N,27.12;S,7.55;1H NMR(400MHz,DMSO-d6):δ2.50(s,3H,CH3),4.52(s,2H,CH2),5.51(s,2H,CH2),7.11(s,2H,NH2),7.96(m,4H,Ar-H),8.00(s,1H,CH),9.28(s,1H,CH).IR(KBr):1271(C=S),1712(C=O),3426(N-H)cm-1.EI-MS(m/z,%):408(M+,2).
实施例5：化合物21的制备
将1mmol2-甲基-4-氨基-5-叠氮甲基嘧啶和1mmol丙炔基苯甲酰基硫脲溶于20mL乙腈中，加入2mmol二异丙基乙基胺和0.1mmol碘化亚铜，在30-40℃搅拌反应10-15小时，TLC（薄层色谱）监测反应至完全，加水有固体析出，经减压过滤、水洗、烘干，得到粗品。用N,N-二甲基甲酰胺和水重结晶，得目标化合物，为浅黄色固体，产率70%，mp：124-126℃。
元素分析/%：计算值：C,53.39;H,4.74;N,29.30;S,8.38;实测值：C,53.04;H,4.65;N,29.27;S,8.35;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.35(s,2H,CH2),5.44(s,2H,CH2),5.66(s,2H,NH2),7.41-8.03(m,5H,Ar-H),7.72(s,1H,CH),8.19(s,1H,CH).IR(KBr):1265(C=S),1692(C=O),3150(N-H),3410cm-1.EI-MS(m/z,%):383(M++1,100).
化合物22-40按化合物21类似方法制得，其结构鉴定数据如下：
化合物22
所得纯品为黄色固体，产率87%，m.p.115-116℃。元素分析/%：计算值：C,48.98;H,4.11;N,26.88;S,7.69;实测值：C,49.20;H,4.36;N,26.79;S,7.74;1H NMR(400MHz,CDCl3):δ2.50(s,3H,CH3),5.36(s,2H,CH2),5.45(s,2H,CH2),5.58(s,2H,NH2),7.28-7.85(m,4H,Ar-H),7.46(s,1H,CH),8.19(s,1H,CH).IR(KBr):1250(C=S),1717(C=O),3145(N-H),3544cm-1.EI-MS(m/z,%):417(M++1,100).
化合物23
所得纯品为黄色固体，产率85%，m.p.159-161℃。元素分析/%：计算值：C,48.98;H,4.11;N,26.88;S,7.69;实测值：C,48.99;H,4.43;N,26.52;S,7.39;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.38(s,2H,CH2),5.44(s,2H,CH2),5.66(s,2H,NH2),7.35-7.99(m,4H,Ar-H),7.72(s,1H,CH),8.05(s,1H,CH).IR(KBr):1250(C=S),1722(C=O),3147(N-H),3454cm-1.EI-MS(m/z,%):417(M++1,100).
化合物24
所得纯品为黄色固体，产率77%，m.p.124-125℃;元素分析/%：计算值：C,48.98;H,4.11;N,26.88;S,7.69;实测值：C,48.92;H,4.54;N,27.11;S,7.50;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.36(s,2H,CH2),5.43(s,2H,CH2),5.63(s,2H,NH2),7.39-7.97(m,4H,Ar-H),7.71(s,1H,CH),8.20(s,1H,CH).IR(KBr):1250(C=S),1708(C=O),3110(N-H),3452cm-1.EI-MS(m/z,%):417(M++1,100).
化合物25
所得纯品为浅黄色固体，产率80%，m.p.156-157℃。元素分析/%：计算值：C,54.53;H,5.08;N,28.26;S,8.09;实测值：C,49.68;H,4.85;N,28.40;S,8.14;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),2.62(s,3H,CH3),5.36(s,2H,CH2),5.41(s,2H,CH2),5.67(s,2H,NH2),7.22-7.96(m,4H,Ar-H),7.71(s,1H,CH),8.20(s,1H,CH).IR(KBr):1270(C=S),1702(C=O),3150(N-H),3512cm-1.EI-MS(m/z,%):397(M++1,100).
化合物26
所得纯品为黄色固体，产率80%，m.p.120-122℃。元素分析/%：计算值：C,54.53;H,5.08;N,28.26;S,8.09;实测值：C,54.31;H,5.11;N,28.17;S,8.22;1H NMR(400MHz,CDCl3):δ2.51(s,3H,CH3),2.65(s,3H,CH3),5.38(s,2H,CH2),5.43(s,2H,CH2),5.54(s,2H,NH2),7.32-7.93(m,4H,Ar-H),7.71(s,1H,CH),8.08(s,1H,CH).IR(KBr):1270(C=S),1709(C=O),3118(N-H),3452cm-1.EI-MS(m/z,%):397(M++1,100).
化合物27
所得纯品为浅黄色固体，产率90%，m.p.141-143℃。元素分析/%：计算值：C,50.99;H,4.28;N,27.98;S,8.01;实测值：C,50.76;H,4.06;N,27.84;S,8.26;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.36(s,2H,CH2),5.46(s,2H,CH2),5.60(s,2H,NH2),7.11-7.93(m,4H,Ar-H),7.52(s,1H,CH),8.20(s,1H,CH).IR(KBr):1270(C=S),1729(C=O),3148(N-H),3453cm-1.EI-MS(m/z,%):401(M++1,100).
化合物28
所得纯品为黄色固体，产率78%，m.p.152-153℃。元素分析/%：计算值：C,50.99;H,4.28;N,27.98;S,8.01;实测值：C,51.03;H,4.01;N,27.84;S,8.26;1H NMR(400MHz,CDCl3):δ2.50(s,3H,CH3),5.36(s,2H,CH2),5.43(s,2H,CH2),5.62(s,2H,NH2),7.10-8.06(m,4H,Ar-H),7.71(s,1H,CH),8.20(s,1H,CH).IR(KBr):1270(C=S),1721(C=O),3111(N-H),3454cm-1.EI-MS(m/z,%):401(M++1,100).
化合物29
所得纯品为黄色固体，产率86%，m.p.134-136℃。元素分析/%：计算值：C,44.26;H,3.71;N,24.29;S,6.95;实测值：C,44.04;H,3.97;N,24.11;S,6.83;1H NMR(400MHz,CDCl3):δ2.50(s,3H,CH3),5.36(s,2H,CH2),5.45(s,2H,CH2),5.61(s,2H,NH2),7.33-7.80(m,4H,Ar-H),7.66(s,1H,CH),8.20(s,1H,CH).IR(KBr):1270(C=S),1721(C=O),3145(N-H),3453cm-1.EI-MS(m/z,%):462(M++1,100).
化合物30
所得纯品为黄色固体，产率65%，m.p.165-167℃。元素分析/%：计算值：C,48.80;H,3.85;N,26.78;S,7.66;实测值：C,48.65;H,3.82;N,26.88;S,7.82;1H NMR(400MHz,CDCl3):δ2.49(s,3H,CH3),5.36(s,2H,CH2),5.42(s,2H,CH2),5.59(s,2H,NH2),6.92-7.71(m,4H,Ar-H),7.71(s,1H,CH),8.20(s,1H,CH).IR(KBr):1270(C=S),1725(C=O),3139(N-H),3440cm-1.EI-MS(m/z,%):419(M++1,100).
化合物31
所得纯品为黄色固体，产率42%，m.p.240-242℃。元素分析/%：计算值：C,44.21;H,3.49;N,27.29;S,6.94;实测值：C,44.55;H,3.67;N,27.46;S,6.62;1H NMR(600MHz,DMSO-d6):δ2.29(s,3H,CH3),4.48(s,2H,J=6.0Hz,CH2),5.48(s,2H,CH2),6.97(s,2H,NH2),7.68(d,1H,J=8.4Hz,Ar-H),8.02(s,1H,CH),8.21(d,1H,J=8.4Hz,Ar-H),8.32(s,1H,Ar-H),9.23(s,1H,CH).IR(KBr):1355(C=S),1679(C=O),3218(N-H)cm-1.EI-MS(m/z,%):461(M+,2).
化合物32
所得纯品为黄色固体，产率50%，m.p.186-188℃。元素分析/%：计算值：C,45.24;H,3.57;N,24.83;S,7.10;实测值：C,45.02;H,3.30;N,24.00;S,7.46;1H NMR(400MHz,DMSO-d6):δ2.29(s,3H,CH3),4.48(s,2H,J=6.0Hz,CH2),5.63(s,2H,CH2),7.08(s,2H,NH2),7.48(s,2H,Ar-H),7.68(s,1H,Ar-H),8.02(s,1H,Ar-H),8.32(s,1H,Ar-H),9.23(s,1H,CH).IR(KBr):1299(C=S),1666(C=O),3363(N-H)cm-1.EI-MS(m/z,%):450(M+,2).
化合物33
所得纯品为黄色固体，产率62%，m.p.208-209℃。元素分析/%：计算值：C,51.57;H,5.01;N,25.32;S,7.25;实测值：C,51.22;H,5.47;N,25.04;S,7.48;1H NMR(400MHz,DMSO-d6):δ2.30(s,3H,CH3),3.82(s,6H,OCH3),4.47(s,2H,CH2),5.42(s,2H,CH2),6.97(s,2H,NH2),7.04(s,2H,Ar-H),7.60(s,2H,Ar-H),8.02(s,1H,Ar-H),8.32(s,1H,Ar-H),9.12(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ27.4,34.7,47.2,56.0,113.7,127.1,128.9,130.0,131.0,132.3,134.4,135.1,138.3,140.6,160.3,161.1,165.3,169.2,192.4.IR(KBr):1267(C=S),1695(C=O),3334(N-H)cm-1.EI-MS(m/z,%):442(M+,2).
化合物34
所得纯品为黄色固体，产率44%，m.p.181-183℃。元素分析/%：计算值：C,43.22;H,3.41;N,29.65;S,6.79;实测值：C,42.48;H,3.47;N,29.76;S,6.52;1H NMR(400MHz,DMSO-d6):δ2.28(s,3H,CH3),4.57(s,2H,CH2),5.42(s,2H,CH2),6.93(s,2H,NH2),8.07(s,1H,CH),8.95(s,1H,Ar-H),9.07(s,2H,Ar-H),9.75(s,1H,CH).IR(KBr):1344(C=S),1672(C=O),3414(N-H)cm-1.EI-MS(m/z,%):472(M+,2).
化合物35
所得纯品为黄色固体，产率34%，m.p.191-193℃。元素分析/%：计算值：C,51.57;H,5.01;N,25.32;S,7.25;实测值：C,50.60;H,5.42;N,25.17;S,7.05;1H NMR(400MHz,DMSO-d6):δ2.32(s,3H,CH3),3.75(s,3H,OCH3),3.78(s,3H,OCH3),4.85(s,2H,CH2),5.48(s,2H,CH2),6.97(s,2H,NH2),6.67-7.34(m,3H,Ar-H),8.13(s,1H,CH),11.00(s,1H,NH),11.76(s,1H,NH).IR(KBr):1288(C=S),1631(C=O),3432(N-H)cm-1.EI-MS(m/z,%):442(M+,5).
化合物36
所得纯品为黄色固体，产率97%，m.p.228-230℃。元素分析/%：计算值：C,48.80;H,3.85;N,26.78;S,7.66;实测值：C,48.63;H,3.73;N,26.13;S,7.48;1H NMR(400MHz,DMSO-d6):δ2.30(s,3H,CH3),4.48(d,2H,J=5.2Hz,CH2),5.43(s,2H,CH2),6.94(s,2H,NH2),7.14-7.71(m,3H,Ar-H),8.00(s,1H,CH),8.83(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ25.2,46.6,67.0,104.2,104.5,104.8,111.6,111.8,120.2,120.4,123.0,131.8,131.9,144.8,158.5,158.6,161.0,161.1,161.4,162.1,162.2,162.8,164.7.IR(KBr):1432(C=S),1663(C=O),3309(N-H)cm-1.EI-MS(m/z,%):442(M+,5).
化合物37
所得纯品为黄色固体，产率45%，m.p.164-166℃。元素分析/%：计算值：C,45.24;H,3.57;N,24.83;S,7.10;实测值：C,45.60;H,3.44;N,24.13;S,7.36;1H NMR(400MHz,DMSO-d6):δ2.32(s,3H,CH3),4.39(s,2H,CH2),5.51(s,2H,CH2),7.06(s,2H,NH2),7.53-7.81(m,3H,Ar-H),8.25(s,1H,CH).IR(KBr):1431(C=S),1644(C=O),3428(N-H)cm-1.EI-MS(m/z,%):450(M+,2).
化合物38
所得纯品为黄色固体，产率为30%，m.p.206-208℃。元素分析/%：计算值：C,40.17;H,3.37;N,22.04;S,6.31;实测值：C,40.32;H,3.55;N,22.77;S,6.19;1H NMR(400MHz,DMSO-d6):δ2.30(s,3H,CH3),4.43(s,2H,CH2),5.44(s,2H,CH2),6.98(s,2H,NH2),7.16-7.85(m,4H,Ar-H),8.00(s,1H,CH),8.91(s,1H,CH).IR(KBr):1389(C=S),1664(C=O),3335(N-H)cm-1.EI-MS(m/z,%):508(M+,2).
化合物39
所得纯品为黄色固体，产率40%，m.p.230-232℃。元素分析/%：计算值：C,48.00;H,3.80;N,24.88;S,7.12;实测值：C,48.18;H,3.95;N,24.44;S,7.55;1H NMR(400MHz,DMSO-d6):δ2.29(s,3H,CH3),4.52(s,2H,CH2),5.39(s,2H,CH2),6.91(s,2H,NH2),7.85(s,2H,Ar-H),8.02(s,2H,Ar-H),8.04(s,1H,CH),9.26(s,1H,CH).IR(KBr):1336(C=S),1631(C=O),3423(N-H)cm-1.EI-MS(m/z,%):450(M+,2).
化合物40
所得纯品为黄色固体，产率35%，m.p.193-195℃。元素分析/%：计算值：C,53.06;H,4.21;N,30.94;S,7.87;实测值：C,53.14;H,4.06;N,30.01;S,7.65;1H NMR(400MHz,DMSO-d6):δ2.40(s,3H,CH3),4.51(s,2H,CH2),5.46(s,2H,CH2),7.02(s,2H,NH2),7.99(m,4H,Ar-H),7.99(s,2H,Ar-H),9.28(s,1H,CH).IR(KBr):1285(C=S),1663(C=O),3416(N-H)cm-1.EI-MS(m/z,%):407(M+,2).
实施例6：化合物41的制备
于50mL圆底烧瓶中加入2.0mmol2-甲基-4-氨基-5-叠氮甲基嘧啶、2.0mmol三乙胺、10mL无水乙腈、2.1mmol5-苯基-（1,3,4-噻二唑）-2-硫基丙炔，搅拌溶解，再加入0.1mmol的CuI，室温下搅拌反应，TLC（薄层色谱）监测反应至完全，加水搅拌有固体析出，抽滤、水洗、烘干的粗品经乙醇重结晶，得目标化合物，为白色固体，产率91%，mp：121-123℃。
1H NMR(600MHz,DMSO-d6)δ(ppm):2.32(s,3H,CH3),4.65(s,2H,-SCH2-),5.44(s,2H,CH2),7.04(s,2H,NH2),7.58-7.97(m,5H,H-Ph),8.16(s,1H,pyrimidin-5-yl-H);IR(KBr):ν3385(N-H),3140,2361,2356,1663,1594,1574,1471,1430,1224,1195,1120,1064,995,837,814,780,706;HRMS(calcd.)[M+Na]+:419.0837(419.0740).
化合物42-74按化合物41类似方法制得，其结构鉴定数据如下：
化合物42
所得纯品为黄色固体，产率90%，m.p.128-130℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),4.63(s,2H,-SCH2-),5.42(s,2H,CH2),6.93(s,2H,NH2),7.57-8.25(m,4H,1H,H3,5and6-Ph,pyrimidin-5-yl-H);IR(KBr):3337(N-H),3196,2369,2359,2100,1600,1564(N=O),1466,1345(N=O),1260,1228,1194,1121,1089,1048,855,807,725。
化合物43
所得纯品为黄色固体，产率91%;m.p.137-139℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.28(s,3H,CH3),4.66(s,2H,-SCH2-),5.41(s,2H,CH2),6.91(s,2H,NH2),8.14(s,1H,pyrimidin-5-yl-H),8.20-8.43(m,4H,H2,3,5and6-Ph);IR(KBr):3400(N-H),3142,2363,2354,1632,1595,1558,1521(N=O),1463,1346(N=O),1190,1115,1069,855,808,790,708;HRMS(calcd.)[M+Na]+:464.0688(464.0695).
化合物44
所得纯品为白色固体，产率91%;m.p.157-160℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),4.63(s,2H,-SCH2-),5.43(s,2H,CH2),6.97(s,2H,NH2),7.55-7.95(m,4H,H3,4,5and6-Ph),8.14(s,1H,pyrimidin-5-yl-H);IR(KBr):3379(N-H),3140,2364,2355,1660,1595,1572,1478,1431,1196,1120,1091,1050,814,779,762,729;HRMS(calcd.)[M+Na]+:453.0447(453.0393).
化合物45
所得纯品为白色固体，产率91%;m.p.169-171℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.30(s,3H,CH3),4.62(s,2H,-SCH2-),5.42(s,2H,CH2),6.93(s,2H,NH2),6.93-7.40(m,4H,H2,3,5and6-Ph),8.13(s,1H,pyrimidin-5-yl-H);IR(KBr):3334(N-H),3162,2364,2359,1664,1593,1571,1472,1426,1222,1197,1118,1094,1068,1054,839,813,782,729。
化合物46
所得纯品为黄色固体，产率92%;m.p.117-120℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),4.63(s,2H,-SCH2-),5.42(s,2H,CH2),6.93(s,2H,NH2),7.93-8.19(m,4H,1H,H3,4,5and6-Ph,pyrimidin-5-yl-H);IR(KBr):3411(N-H),3144,2453,2353,1662,1647,1596,1572,1528(N=O),1465,1432,1352(N=O),1196,1118,1065,996,857,809,789,726;HRMS(calcd.)[M+Na]+:464.0688(464.0676).
化合物47
所得纯品为白色固体，产率93%;m.p.133-135℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),4.63(s,2H,-SCH2-),5.42(s,2H,CH2),6.93(s,2H,NH2),7.07-7.63(m,3H,H3,5and6-Ph),8.13(s,1H,pyrimidin-5-yl-H);IR(KBr):3327(N-H),3167,2394,2354,1658,1593,1568,1474,1426,1373,1194,1148,1118,1089,1051,864,813,777,731。
化合物48
所得纯品为白色固体，产率93%;m.p.137-139℃;1H NMR(600MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),4.61(s,2H,-SCH2-),5.43(s,2H,CH2),6.96(s,2H,NH2),7.41-7.44(m,2H,H2,6-Ph),7.99-8.00(m,2H,H3,5-Ph),8.13(s,1H,pyrimidin-5-yl-H);IR(KBr):3334(N-H),3150,2432,2354,1665,1609,1594,1573,1501,1473,1426,1357,1228,1192,1119,1066,845,814,781,732;HRMS(calcd.)[M+Na]+:437.0743(437.0713)。
化合物49
所得纯品为白色固体，产率91%;m.p.115-117℃;1H NMR(600MHz,DMSO-d6)δ(ppm):2.28(s,3H,CH3),4.65(s,2H,-SCH2-),5.41(s,2H,CH2),6.94(s,2H,NH2),7.96-7.98(m,2H,H2,6-Ph),8.13-8.15(m,3H,H3,5-Ph,pyrimidin-5-yl-H);IR(KBr):3389(N-H),3069,2400,2354,1664,1595,1558,1505,1468,1416,1324,1197,1166,1111,1077,1058,857,812,791;HRMS(calcd.)[M+Na]+:487.0711(487.0722).
化合物50
所得纯品为黄色固体，产率85%;m.p.144-147℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.30(s,3H,CH3),4.65(s,2H,-SCH2-),5.43(s,2H,CH2),6.91(s,2H,NH2),7.55-7.78(m,3H,H2,4and6-Ph),8.15(s,1H,pyrimidin-5-yl-H);IR(KBr):3364(N-H),3222,2363,2354,1633,1598,1561,1531(N=O),1470,1346,(N=O)1283,1235,1180,1102,991,865,811,750,720。
化合物51
所得纯品为黄色固体，产率88%;m.p.151-153℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.28(s,3H,CH3),4.67(s,2H,-SCH2-),5.42(s,2H,CH2),6.94(s,2H,NH2),7.87(s,1H,H1-Ph),8.15(s,1H,pyrimidin-5-yl-H),8.35-8.63(m,3H,H4,5and6-Ph);IR(KBr):3370(N-H),2355,2335,1629,1597,1557,1528(N=O),1462,1433,1352(N=O),1229,1198,1113,1058,972,871,811,789,744,709;HRMS(calcd.)[M+Na]+:464.0688(464.0638)。
化合物52
所得纯品为白色固体，产率90%;m.p.139-141℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.31(s,3H,CH3),4.63(s,2H,-SCH2-),5.48(s,2H,CH2),7.02(s,2H,NH2),7.40-7.99(m,4H,H3,4,5and6-Ph),8.15(s,1H,pyrimidin-5-yl-H);IR(KBr):3401(N-H),3132,2440,2356,1666,1600,1564,1493,1477,1437,1337,1222,1183,1118,1054,814,790,771,736;HRMS(calcd.)[M+Na]+:437.0743(437.0700).
化合物53
所得纯品为黄色固体，产率为70%;m.p.170-171℃;元素分析/%：计算值：C,42.95;H,3.18;N,23.57;S,13.49;实测值：C,43.36;H,3.39;N,23.21;S,13.14;1HNMR(400MHz,DMSO-d6(ppm):2.28(s,3H,CH3),4.62(s,2H,-SCH2-),5.41(s,2H,CH2),6.91(s,2H,NH2),7.54-7.58(m,2H,H-Ph),7.84-7.89(m,2H,H-Ph),8.02(s,1H,1,2,3-triazol-4-yl-H);8.14(s,1H,pyrimidin-5-yl-H),13CNMR(100MHz,DMSO-d6)δ(ppm):25.4,26.9,47.0,109.7,120.9,124.4,128.5,131.8,133.6,134.6,142.6,148.1,156.3,161.6,164.3。
化合物54
所得纯品为浅黄色固体，产率52%;m.p.180-182℃;元素分析/%：计算值：C,50.69;H,4.25;N,26.27;S,15.04;实测值：C,50.42;H,4.46;N,26.24;S,15.15;1H NMR(400MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),3.84(s,3H,OCH3),4.61(s,2H,-SCH2-),5.42(s,2H,CH2),6.94(s,2H,NH2),7.13(d,2H,J=10.8Hz,Ar-H),7.89(d,2H,J=10.8Hz,Ar-H),8.14(s,1H,pyrimidin-5-yl-H)。
化合物55
所得纯品为浅黄色固体，产率71%;m.p.209-211℃;元素分析/%：计算值：C,52.66;H,4.42;N,27.30;S,15.62;实测值：C,52.68;H,4.49;N,27.27;S,15.48;1H NMR(400MHz,DMSO-d6)δ(ppm):2.28(s,3H,CH3),2.38(s,3H,CH3),4.61(s,2H,-SCH2-),5.40(s,2H,CH2),6.93(s,2H,NH2),7.39(d,2H,J=8.0Hz,Ar-H),7.84(d,2H,J=8.0Hz,Ar-H),7.98(s,1H,1,2,3-triazol-4-yl-H),8.14(s,1H,pyrimidin-5-yl-H)。
化合物56
所得纯品为棕色固体，产率62%;m.p.155-156℃;元素分析/%：计算值：C,52.66;H,4.42;N,27.30;S,15.62;实测值：C,51.90;H,4.85;N,26.66;S,15.39;1H NMR(600MHz,DMSO-d6)δ(ppm):2.39(s,3H,CH3),2.61(s,3H,CH3),4.75(s,2H,-SCH2-),5.52(s,2H,CH2),7.05(s,2H,NH2),7.55-7.59(m,2H,Ar-H),7.86-7.90(m,2H,Ar-H),8.08(s,1H,1,2,3-triazol-4-yl-H),8.25(s,1H,pyrimidin-5-yl-H)。
化合物57
所得纯品为浅黄色固体，产率74%;m.p.149-151℃;1H NMR(600MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),2.57(s,3H,CH3),4.64(s,2H,-SCH2-),5.42(s,2H,CH2),6.95(s,2H,NH2),7.41(d,2H,J=27.0Hz,H-Ph),7.49(d,H,H-Ph),7.85(d,2H,J=7.2Hz,Ar-H),7.90(s,1H,1,2,3-triazol-4-yl-H),8.06(s,1H,pyrimidin-5-yl-H)。
化合物58
所得纯品为黄色固体，产率93%;m.p.162-164℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.32(s,3H,CH3),4.64(s,2H,-SCH2-),5.42(s,2H,CH2),7.00(s,2H,NH2),7.52-7.99(m,3H,H3,5and6-Ph),8.13(s,1H,pyrimidin-5-yl-H);IR(KBr):3356(N-H),3132,2355,2332,2097,1629,1594,1559(N=O),1467,1345(N=O),1260,1227,1193,1089,1050,883,806,729。
化合物59
所得纯品为黄色固体，产率90%;m.p.143-145℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.31(s,3H,CH3),4.63(s,2H,-SCH2-),5.44(s,2H,CH2),6.97(s,2H,NH2),7.91-8.18(m,4H,1H,H3,4,5and6-Ph,pyrimidin-5-yl-H);13C NMR(100MHz,DMSO-d6)δ(ppm):25.11,26.86,46.78,108.35,123.92,124.56,127.74,128.48,142.25,149.15,155.89,161.45,163.98,164.51,167.18;HRMS(calcd.)[M+H]+:426.1097(426.1102).
化合物60
所得纯品为黄色固体，产率86%;m.p.126-128℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.31(s,3H,CH3),4.63(s,2H,-SCH2-),5.44(s,2H,CH2),6.97(s,2H,NH2),7.08-7.41(m,4H,H3,4,5and6-Ph),8.11(s,1H,pyrimidin-5-yl-H);IR(KBr):3382(N-H),3141,2355,2334,1660,1595,1572,1468,1431,1359,1196,1120,1091,1071,1051,998,863,815,779,763,729;HRMS(calcd.)[M+H]+:415.0856(415.0831).
化合物61
所得纯品为白色固体，产率93%;m.p.189-191℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.31(s,3H,CH3),4.63(s,2H,-SCH2-),5.44(s,2H,CH2),6.97(s,2H,NH2),6.93-7.40(m,4H,H2,3,5and6-Ph),8.13(s,1H,pyrimidin-5-yl-H);IR(KBr):3337(N-H),3157,2462,2357,1664,1591,1570,1475,1426,1406,1222,1197,1117,1095,1068,1053,1012,839,813,782,729;HRMS(calcd.)[M+H]+:415.0856(415.0890)。
化合物62
所得纯品为黄色固体，产率90%;m.p.171-173℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.31(s,3H,CH3),4.63(s,2H,-SCH2-),5.44(s,2H,CH2),6.97(s,2H,NH2),7.91-8.18(m,4H,1H,H3,4,5and6-Ph,pyrimidin-5-yl-H);IR(KBr):3415(N-H),3145,2353,1648,1597,1569,1527(N=O),1465,1431,1352(N=O),1195,1118,1065,986,857,808,751,725;HRMS(calcd.)[M+H]+:426.1097(426.1082).
化合物63
得纯品为白色固体，产率91%;m.p.173-175℃;1H NMR(600MHz,DMSO-d6)δ(ppm):2.31(s,3H,CH3),4.64(s,2H,-SCH2-),5.45(s,2H,CH2),7.00(s,2H,NH2),7.63-7.97(m,3H,H3,5and6-Ph),8.15(s,1H,pyrimidin-5-yl-H);IR(KBr):3336(N-H),3174,2418,2360,1657,1594,1568,1475,1430,1217,1195,1119,1090,1052,1037,865,832,814,778,732;HRMS(calcd.)[M+Na]+:471.0286(471.0320).
化合物64
所得纯品为白色固体，产率89%;132-134℃;1H NMR(600MHz,DMSO-d6)δ(ppm):2.31(s,3H,CH3),4.63(s,2H,-SCH2-),5.43(s,2H,CH2),7.01(s,2H,NH2),7.40-7.44(m,2H,H2,6-Ph),7.99-8.01(m,2H,H3,5-Ph),8.15(s,1H,pyrimidin-5-yl-H);IR(KBr):3428(N-H),3152,2360,2357,1665,1595,1574,1502,1474,1426,1228,1192,1158,1121,1067,997,956,846,815,782,733;HRMS(calcd.)[M+H]+:399.1152(399.1151).
化合物65
所得纯品为白色固体，产率89%;132-134℃;1H NMR(600MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),4.66(s,2H,-SCH2-),5.42(s,2H,CH2),6.98(s,2H,NH2),7.96-7.97(m,2H,H2,6-Ph),8.14-8.16(m,3H,H3,5-Ph,pyrimidin-5-yl-H);IR(KBr):3423(N-H),3069,2360,2357,1665,1595,1559,1508,1468,1416,1325,1198,1167,1110,1077,1058,1015,857,812,792;HRMS(calcd.)[M+H]+:449.1120(449.1133).
化合物66
所得纯品为白色固体，产率88%;m.p.138-140℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.37(s,3H,CH3),4.66(s,2H,-SCH2-),5.47(s,2H,CH2),7.10(s,2H,NH2),7.58-7.95(m,5H,H-Ph),8.18(s,1H,pyrimidin-5-yl-H);HRMS(calcd.)[M+H]+:381.1246(381.1236)。
化合物67
所得纯品为黄色固体，产率87%;m.p.163-165℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.31(s,3H,CH3),4.65(s,2H,-SCH2-),5.43(s,2H,CH2),6.97(s,2H,NH2),7.52-7.75(m,3H,H2,4and6-Ph),8.14(s,1H,pyrimidin-5-yl-H);IR(KBr):3369(N-H),3230,2366,2359,1640,1595,1567,1544(N=O),1472,1351(N=O),1279,1231,1180,1102,990,868,811,750,723。
化合物68
所得纯品为黄色固体，产率90%;m.p.171-173℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.28(s,3H,CH3),4.66(s,2H,-SCH2-),5.43(s,2H,CH2),6.91(s,2H,NH2),7.89(s,1H,H1-Ph),8.14(s,1H,pyrimidin-5-yl-H),8.41-8.65(m,3H,H4,5and6-Ph);IR(KBr):3399(N-H),3132,2362,2355,1660,1593,1562,1527(N=O),1471,1353(N=O),1233,1123,1063,994,868,813,742,710;HRMS(calcd.)[M+H]+:426.1097(426.1069)。
化合物69
所得纯品为白色固体，产率90%;m.p.165-168℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.31(s,3H,CH3),4.62(s,2H,-SCH2-),5.43(s,2H,CH2),7.08(s,2H,NH2),7.41-7.97(m,4H,H3,4,5and6-Ph),8.13(s,1H,pyrimidin-5-yl-H);IR(KBr):3401(N-H),3133,2440,1665,1619,1598,1565,1494,1476,1438,1338,1223,1185,1119,1054,994,959,813,790,770,737;HRMS(calcd.)[M+H]+:399.1152(399.1143).
化合物70
所得纯品为棕色固体，产率72%;m.p.167-168℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),4.64(s,2H,-SCH2-),5.42(s,2H,CH2),6.94(s,2H,NH2),7.56(s,2H,H-Ph),7.88(s,2H,H-Ph),8.01(s,1H,1,2,3-triazol-4-yl-H),8.15(s,1H,pyrimidin-5-yl-H)。
化合物71
所得纯品为浅黄色固体，产率88%;m.p.180-181℃;元素分析/%：计算值：C,52.67;H,4.42;N,27.30;O,7.80;S,7.81;实测值：C,52.38;H,4.16;N,27.63;S,7.83;1H NMR(600MHz,DMSO-d6)δ(ppm):2.28(s,3H,CH3),3.84(s,3H,OCH3),4.60(s,2H,-SCH2-),5.40(s,2H,CH2),6.93(s,2H,NH2),7.11(d,2H,J=12Hz,Ar-H),7.88(d,2H,J=12Hz,Ar-H),7.98(s,1H,1,2,3-triazol-4-yl-H),8.15(s,1H,pyrimidin-5-yl-H)。
化合物72
所得纯品为浅黄色固体，产率79%;m.p.215-217℃;1H NMR(400MHz,DMSO-d6)δ(ppm):2.40(s,3H,CH3),2.61(s,3H,CH3),4.73(s,2H,-SCH2-),5.52(s,2H,CH2),7.04(s,2H,NH2),7.52(s,2H,H-Ph),7.95(d,2H,J=5.6Hz,Ar-H),8.08(s,1H,1,2,3-triazol-4-yl-H),8.27(s,1H,pyrimidin-5-yl-H)。
化合物73
所得纯品为棕色固体，产率85%;m.p.152-153℃;元素分析/%：计算值：C,54.81;H,4.60;N,28.41;S,8.13;实测值：C,54.59;H,4.85;N,27.94;S,8.20;1H NMR(600MHz,DMSO-d6)δ(ppm):2.40(s,3H,CH3),2.62(s,3H,CH3),4.75(s,2H,-SCH2-),5.52(s,2H,CH2),7.05(s,2H,NH2),7.56-7.60(m,2H,Ar-H),7.87-7.91(m,2H,Ar-H),8.07(s,1H,1,2,3-triazol-4-yl-H),8.25(s,1H,pyrimidin-5-yl-H)。
化合物74
所得纯品为棕色固体，产率65%;m.p.152-153℃;元素分析/%：计算值：C,54.81;H,4.60;N,28.41;S,8.13;实测值：C,54.89;H,4.38;N,28.86;S,7.85;1H NMR(600MHz,DMSO-d6)δ(ppm):2.29(s,3H,CH3),2.58(s,3H,CH3),4.63(s,2H,-SCH2-),5.41(s,2H,CH2),6.94(s,2H,NH2),7.39-7.50(m,3H,H-Ph),7.85(d,H,J=8.4Hz,Ar-H),7.96(s,1H,1,2,3-triazol-4-yl-H),8.14(s,1H,pyrimidin-5-yl-H)。
实施例7：化合物75的制备
100mL圆底烧瓶中依次加入1mmol2-甲基-4-氨基-5-叠氮甲基嘧啶、1mmol O-炔丙基-4-氟苯乙酮肟醚、2mmol三乙胺，溶于10mL无水四氢呋喃（THF），室温下搅拌，待固体溶解后，加入0.1mmol碘化亚铜，室温下反应10-15小时，TLC（薄层色谱）反应至完全，加水搅拌有固体析出，减压抽滤、水洗、烘干的粗品，用二甲基甲酰胺（DMF）和水重结晶，得黄色固体，产率71%，mp：96-97℃。
元素分析/%：计算值：C,57.46;H,5.11;N,27.59;实测值：C,57.65;H,5.18;N,27.26;1HNMR(600MHz,DMSO-d6):δ2.14(s,3H,CH3),2.29(s,3H,CH3),5.20(s,2H,CH2),5.44(s,2H,CH2),6.95(s,2H,NH2),7.23(d,2H,J=8.4Hz,Ar-H),7.67(s,2H,J=6.0Hz,Ar-H),8.01(s,1H,CH),8.18(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ12.5,25.2,46.7,66.9,108.4,115.2,115.8,124.6,128.1,128.2,132.3,143.5,153.9,156.2,161.5,164.0,167.2.IR(KBr):1663(C=N),3431(N-H)cm-1.EI-MS(m/z,%):355(M+,11).
化合物76-95按化合物75类似方法制得，其结构鉴定数据如下：
化合物76
所得纯品为黄色固体，产率66%，m.p.180-183℃;元素分析/%：计算值：C,49.05;H,4.36;N,23.55;实测值：C,49.23;H,4.54;N,23.91;1H NMR(600MHz,DMSO-d6):δ2.13(s,3H,CH3),2.29(s,3H,CH3),5.20(s,2H,CH2),5.49(s,2H,CH2),7.02(s,2H,NH2),7.56-7.61(m,4H,Ar-H),8.19(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ12.5,25.5,46.7,66.9,111.0,122.6,124.6,127.8,130.0,131.3,134.8,143.5,155.7,161.3,168.7.IR(KBr):1674(C=N),3296(N-H)cm-1.EI-MS(m/z,%):415(M+,7).
化合物77
所得纯品为黄色固体，产率90%，m.p.184-186℃;元素分析/%：计算值：C,54.91;H,4.88;N,26.37;实测值：C,54.45;H,4.75;N,26.18;1H NMR(600MHz,DMSO-d6):δ2.14(s,3H,CH3),2.30(s,3H,CH3),5.20(s,2H,CH2),5.44(s,2H,CH2),6.98(s,2H,NH2),7.47(s,2H,Ar-H),7.64(s,2H,Ar-H),8.19(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ12.5,25.5,46.7,66.9,111.0,122.6,124.6,127.8,130.0,131.3,134.8,143.5,155.7,161.3,168.7.IR(KBr):1676(C=N),3299(N-H)cm-1.EI-MS(m/z,%):371(M+,7).
化合物78
所得纯品为黄色固体，产率73%，m.p.131-132℃;元素分析/%：计算值：C,60.52;H,5.68;N,29.06;实测值：C,59.85;H,5.65;N,29.35;1H NMR(600MHz,DMSO-d6):δ2.15(s,3H,CH3),2.29(s,3H,CH3),5.20(s,2H,CH2),5.44(s,2H,CH2),6.98(s,2H,NH2),7.40(d,2H,J=2.4Hz,Ar-H),7.63(d,2H,J=3.0Hz,Ar-H),8.01(s,1H,Ar-H),8.19(s,1H,CH);13C NMR(100MHz,DMSO-d6):δ12.5,25.2,46.7,66.8,108.3,124.6,125.9,128.4,129.2,135.8,143.5,154.7,156.2,161.5,167.0.IR(KBr):1664(C=N),3327(N-H)cm-1.EI-MS(m/z,%):337(M+,8).
化合物79
所得纯品为黄色固体，产率64%，m.p.154-156℃;元素分析/%：计算值：C,58.84;H,5.76;N,26.69;实测值：C,58.58;H,5.62;N,26.13;1H NMR(600MHz,DMSO-d6):δ2.12(s,3H,CH3),2.29(s,3H,CH3),3.37(s,3H,OCH3),5.16(s,2H,CH2),5.43(s,2H,CH2),6.94(s,2H,NH2),6.96(s,2H,Ar-H),7.58(d,2H,J=3.0Hz,Ar-H),8.17(s,1H,Ar-H);13C NMR(100MHz,DMSO-d6):δ12.4,25.2,46.6,55.1,66.7,108.4,113.8,124.5,127.3,128.2,143.6,156.2,160.1,161.5,167.0,183.0.IR(KBr):1669(C=N),3323(N-H)cm-1.EI-MS(m/z,%):367(M+,10).
化合物80
所得纯品为黄色固体，产率66%，m.p.222-224℃;元素分析/%:计算值：C,53.40;H,4.74;N,29.30;实测值：C,53.61;H,4.31;N,29.12;1H NMR(600MHz,DMSO-d6):δ2.21(s,3H,CH3),2.30(s,3H,CH3),5.27(s,2H,CH2),5.47(s,2H,CH2),6.98(s,2H,NH),7.89(s,2H,Ar-H),8.21(s,1H,CH),8.25(d,2H,J=7.2Hz,Ar-H);IR(KBr):1673(C=N),3302(N-H)cm-1.
化合物81
所得纯品为黄色固体，产率50%，m.p.126-127℃;元素分析/%：计算值：C,57.46;H,5.11;N,27.59;实测值：C,57.15;H,5.12;N,27.32;1H NMR(600MHz,DMSO-d6):δ2.13(s,3H,CH3),2.30(s,3H,CH3),5.20(s,2H,CH2),5.45(s,2H,CH2),6.98(s,2H,NH),7.22-7.46(s,4H,Ar-H),8.04(s,1H,CH),8.17(s,1H,CH);IR(KBr):1639(C=N),3384(N-H)cm-1。
化合物82
所得纯品为黄色固体，产率67%，m.p.188-190℃;元素分析/%：计算值：C,54.91;H,4.88;N,26.37;实测值：54.18;H,4.72;N,26.46;1H NMR(600MHz,DMSO-d6):δ2.14(s,3H,CH3),2.29(s,3H,CH3),5.20(s,2H,CH2),5.45(s,2H,CH2),6.98(s,2H,NH),7.46(s,2H,Ar-H),7.64(s,2H,Ar-H),8.19(s,1H,CH);IR(KBr):1676(C=N),3297(N-H)cm-1.
化合物83
所得纯品为黄色固体，产率64%，m.p.131-133℃;元素分析/%：计算值：C,54.91;H,4.88;N,26.37;实测值：C,54.48;H,4.62;N,26.26;1H NMR(600MHz,DMSO-d6):δ2.15(s,3H,CH3),2.29(s,3H,CH3),5.22(s,2H,CH2),5.44(s,2H,CH2),6.95(s,2H,NH),7.42-7.48(m,2H,Ar-H),7.60(d,1H,J=7.2Hz,Ar-H),7.67(s,1H,Ar-H),8.00(s,1H,CH),8.19(s,1H,CH);IR(KBr):1670(C=N),3389(N-H)cm-1.
化合物84
所得纯品为黄色固体，产率34%，m.p.109-110℃;元素分析/%：计算值：C,53.40;H,4.74;N,29.30;实测值：C,53.11;H,4.69;N,29.57;1H NMR(600MHz,DMSO-d6):δ2.10(s,3H,CH3),2.30(s,3H,CH3),5.12(s,2H,CH2),5.43(s,2H,CH2),6.95(s,2H,NH),7.56(d,1H,J=7.8Hz,Ar-H),7.67(t,1H,J=7.2Hz,Ar-H),7.78(t,1H,J=7.2Hz,Ar-H),8.00(s,1H,CH),8.02(d,1H,J=8.4Hz,Ar-H),8.11(s,1H,CH);IR(KBr):1669(C=N),3385(N-H)cm-1.
化合物85
所得的纯品为白色固体，产率74%，1H NMR(600MHz,DMSO-d6)δ(ppm):2.10(s,3H,CH3),2.32(s,3H,CH3),5.19(s,2H,CH2),5.46(s,2H,CH2),7.00(s,2H,NH2),7.34(s,1H,Ar-H),7.50(s,1H,Ar-H),7.70(s,1H,Ar-H).IR(KBr)υ(cm-1):3414(NH2),2972(CH3),1667(C=N),1646-1227(Ar).
化合物86
所得纯品为黄色固体，产率70%，m.p.190-192℃;元素分析/%：计算值：C,48.99;H,3.85;N,25.00;实测值：C,48.29;H,3.88;N,25.12;1H NMR(600MHz,DMSO-d6):δ2.30(s,3H,CH3),5.25(s,2H,CH2),5.45(s,2H,CH2),6.95(s,2H,NH),7.49-7.79(m,3H,Ar-H),8.01(s,1H,CH),8.22(s,1H,CH),8.39(s,1H,CH);IR(KBr):1676(C=N),3346(N-H)cm-1.
化合物87
所得纯品为黄色固体，产率78%，m.p.185-187℃;元素分析/%：计算值：C,53.71;H,4.51;N,27.40;实测值：C,53.32;H,4.56;N,27.02;1H NMR(600MHz,DMSO-d6):δ2.28(s,3H,CH3),5.18(s,2H,CH2),5.43(s,2H,CH2),6.94(s,2H,NH),7.48(d,2H,J=8.4Hz,Ar-H),7.61(d,2H,J=8.4Hz,Ar-H),7.94(s,2H,CH),8.19(s,1H,CH),8.25(s,1H,CH)。
化合物88
所得纯品为黄色固体，产率86%，m.p.179-181℃;元素分析/%：计算值：C,47.44;H,4.01;N,24.37;实测值：C,46.95;H,4.10;N,24.21;1H NMR(600MHz,DMSO-d6):δ2.31(s,3H,CH3),3.78(s,3H,CH3),5.15(s,2H,CH2),5.47(s,2H,CH2),6.98(s,2H,NH),6.98(s,4H,Ar-H),7.62(d,2H,J=7.8Hz,Ar-H),7.94(s,1H,CH),8.19(s,1H,CH),8.24(s,1H,CH)。
化合物89
所得纯品为黄色固体，产率74%，m.p.168-170℃;元素分析/%：计算值：C,56.30;H,4.72;N,28.72;实测值：C,56.49;H,4.38;N,28.52;1H NMR(600MHz,DMSO-d6):δ2.30(s,3H,CH3),5.18(s,2H,CH2),5.46(s,2H,CH2),6.99(s,2H,NH),7.26(s,2H,Ar-H),7.94(s,1H,CH),8.19(s,1H,CH),8.25(s,1H,CH)。
化合物90
所得纯品为黄色固体，产率30%，m.p.100-101℃;元素分析/%：计算值：C,57.78;H,5.42;N,27.75;实测值：C,57.30;H,5.41;N,27.56;1H NMR(600MHz,DMSO-d6):δ2.31(s,3H,CH3),3.78(s,3H,OCH3),5.15(s,2H,CH2),5.47(s,2H,CH2),6.98(s,4H,Ar+NH),7.54(s,2H,Ar-H),8.17(s,2H,CH)。
化合物91
所得纯品为黄色固体，产率92%，m.p.170-172℃;元素分析/%：计算值：C,C,59.43;H,5.30;N,30.32;实测值：C,59.65;H,5.44;N,30.24;1H NMR(600MHz,DMSO-d6):δ2.29(s,3H,CH3),5.18(s,2H,CH2),5.44(s,2H,CH2),6.95(s,2H,NH2),7.41-7.59(m,5H,Ar-H),8.02(s,1H,CH),8.19(s,1H,CH),8.24(s,1H,CH)。
化合物92
所得纯品为黄色固体，产率65%，m.p.214-216℃;元素分析/%：计算值：C,52.17;H,4.38;N,30.42;实测值：C,51.72;H,4.23;N,30.89;1H NMR(600MHz,DMSO-d6):δ2.29(s,3H,CH3),5.26(s,2H,CH2),5.43(s,2H,CH2),6.96(s,2H,NH),7.86(d,2H,J=9.0Hz,Ar-H),8.22(s,1H,CH),8.27(d,2H,J=8.4Hz,CH),8.42(s,1H,CH)。
化合物93
所得纯品为黄色固体，产率32%，m.p.180-182℃;元素分析/%：计算值：C,52.17;H,4.38;N,30.42;实测值：C,52.73;H,4.45;N,30.08;1H NMR(600MHz,DMSO-d6):δ2.30(s,3H,CH3),5.32(s,2H,CH2),5.46(s,2H,CH2),6.96(s,2H,NH2),7.10(t,1H,J=7.2Hz,Ar-H),7.46(d,1H,J=8.4Hz,Ar-H),7.67(t,1H,J=7.8Hz,Ar-H),7.32(d,1H,J=7.2Hz,Ar-H),7.98(s,1H,CH),7.99(s,1H,CH),8.27(s,1H,CH)。
化合物94
所得纯品为黄色固体，产率46%，m.p.154-155℃;元素分析/%：计算值：C,53.71;H,4.51;N,27.40;实测值：C,53.51;H,4.58;N,27.69;1H NMR(600MHz,DMSO-d6):δ2.29(s,3H,CH3),5.21(s,2H,CH2),5.44(s,2H,CH2),6.94(s,2H,NH),7.44-7.50(m,2H,Ar-H),7.57(d,1H,J=9.0Hz,Ar-H),7.65(s,2H,CH),7.99(s,1H,CH),8.20(s,1H,CH),8.26(s,1H,CH)。
化合物95
所得纯品为黄色固体，产率46%，m.p.154-155℃;元素分析/%：计算值：C,53.71;H,4.51;N,27.40;实测值：C,53.51;H,4.58;N,27.69;1H NMR(600MHz,DMSO-d6):δ2.29(s,3H,CH3),5.21(s,2H,CH2),5.44(s,2H,CH2),6.94(s,2H,NH),7.44-7.50(m,2H,Ar-H),7.57(d,1H,J=9.0Hz,Ar-H),7.65(s,2H,CH),7.99(s,1H,CH),8.20(s,1H,CH),8.26(s,1H,CH)。
实施例8：化合物96的制备
将1mmol2-甲基-4-氨基-5-叠氮甲基嘧啶和1mmol碘代-O-炔丙基-4-氯苯乙酮肟醚溶于5mL无水乙腈，加入0.1mmol碘化亚铜和2mmol三乙胺，室温条件下搅拌反应12小时，加水搅拌有固体析出，抽滤、干燥得黄色固体，产率72%；1H NMR(600MHz,DMSO-d6)δ(ppm):2.16(s,3H,CH3),2.30(s,3H,CH3),5.17(s,2H,CH2),5.45(s,2H,CH2),6.90(s,2H,NH2),7.44(d,2H,J=8.4Hz,Ar-H),7.66(d,2H,J=8.4,Ar-H).
化合物97-104按化合物96类似方法制得，其结构鉴定数据如下：
化合物97
所得纯品为白色固体，产率75%，
1H NMR(600MHz,DMSO-d6)δ(ppm):2.16(s,3H,CH3),2.30(s,3H,CH3),5.16(s,2H,CH2),5.46(s,2H,CH2),6.90(s,2H,NH2),7.22(s,2H,Ar-H),7.70(s,2H,Ar-H).
化合物98
所得纯品为白色固体，产率69%，1H NMR(600MHz,DMSO-d6)δ(ppm):2.13(s,3H,CH3),2.29(s,3H,CH3),5.15(s,2H,CH2),5.43(s,2H,CH2),6.90(s,2H,NH2),7.42(s,2H,Ar-H),7.64(s,2H,Ar-H).
化合物99
所得纯品为白色固体，产率79%，1H NMR(600MHz,DMSO-d6)δ(ppm):2.16(s,3H,CH3),2.31(s,3H,CH3),5.16(s,2H,CH2),5.46(s,2H,CH2),6.96(s,2H,NH2),7.39(s,3H,Ar-H),7.65(s,2H,Ar-H).
化合物100
所得的纯品为白色固体，产率81%，1H NMR(600MHz,DMSO-d6)δ(ppm):2.22(s,3H,CH3),2.33(s,3H,CH3),5.24(s,2H,CH2),5.49(s,2H,CH2),6.94(s,2H,NH2),7.91(d,2H,J=7.8Hz,Ar-H),8.23(d,2H,J=8.4Hz,Ar-H).
化合物101
所得的纯品为白色固体，产率80%，
1H NMR(600MHz,DMSO-d6)δ(ppm):2.16(s,3H,CH3),2.30(s,3H,CH3),5.18(s,2H,CH2),5.44(s,2H,CH2),6.91(s,2H,NH2),7.42(s,1H,Ar-H),7.47(s,1H,Ar-H),7.62(s,1H,Ar-H),7.69(s,1H,Ar-H).EI-MS(m/z,%):497(M+,5.21).
化合物102
所得的纯品为白色固体，产率76%，1H NMR(600MHz,DMSO-d6)δ(ppm):2.15(s,3H,CH3),2.31(s,3H,CH3),5.17(s,2H,CH2),5.45(s,2H,CH2),6.91(s,2H,NH2),7.58(s,4H,Ar-H).
化合物103
所得的纯品为白色固体，产率78%，1H NMR(600MHz,DMSO-d6)δ(ppm):2.15(s,3H,CH3),2.31(s,3H,CH3),5.17(s,2H,CH2),5.44(s,2H,CH2),6.91(s,2H,NH2),7.22(d,1H,J=7.8Hz,Ar-H),7.25(d,1H,J=8.4Hz,Ar-H),7.43-7.46(t,2H,J=7.8Hz,7.2Hz,Ar-H),7.65(s,1H,pyrimidine CH).
化合物104
所得的纯品为白色固体，产率74%，1H NMR(600MHz,DMSO-d6)δ(ppm):2.10(s,3H,CH3),2.32(s,3H,CH3),5.19(s,2H,CH2),5.46(s,2H,CH2),7.00(s,2H,NH2),7.34(s,1H,Ar-H),7.50(s,1H,Ar-H),7.70(s,1H,Ar-H).
上述实施例合成的化合物见表1。
表1合成的化合物
本发明具有通式（I）结构的化合物具有优异的杀菌活性，能用于防治小麦赤霉病菌、水稻纹枯病菌、黄瓜灰霉病菌、番茄早疫病菌、烟草赤星病菌和黄瓜炭疽病菌，部分化合物对真菌的防治效果与对照商品化杀菌剂相当或更好。
实施例9杀菌活性试验
以菌丝的生长速率为依据来测定杀菌活性。选取与经济作物、蔬菜类作物、水果类作物有关的六种常见菌类：水稻纹枯病、黄瓜灰霉病、小麦赤霉病、番茄早疫病、烟草赤星病和黄瓜炭疽病作为供试靶标。本发明化合物用丙酮溶解，吐温-80乳化，加入蒸馏水配成一定浓度药液待用。马铃薯200克，葡萄糖15克，琼脂15克，水1000克配成培养基后，于直径9cm的培养皿高温减压灭菌25min，灭菌后趁热将培养基13.5mL和药液1.5mL混合均匀等分到两个培养皿中，水平放置，待冷却后，用灭过菌的取菌器分别从菌种的培养液中取5mm带菌琼脂，放入各培养皿中菌丝面向下，每皿放2-3种菌。设两组空白对照，然后置于无菌恒温干燥箱内48小时，测定菌斑的直径根据空白对照，以直径表示药效：抑制率%=（对照-处理）/对照×100%。
实验材料：
供试菌种：小麦赤霉病菌(Gibberella zeae)、黄瓜灰霉病菌(Botrytis cinerea)、番茄早疫病菌(Alternaria solania)、烟草赤星病菌(Alternaria alternata(Fries)Keissler)、黄瓜炭疽病菌(GloeosporiumorbiculareArs)。
测试结果见表2。
表2部分化合物的测试结果（测试浓度100μg/g）
文中涉及的文献如下：
文献1：Karl M.Erixon,Chester L.Dabalos,Finian J.Leeper.Synthesis and biological evaluation ofpyrophosphate mimics of thiamine pyrophosphate based on a triazole scaffold.Organic&BiomolecularChemistry,2008,6,3561-3572.

Claims (9)

1.具有杀菌活性的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物，其特征在于为具有通式（I）结构的化合物：
其中：
R1表示氢或I；
X表示O、NH或S；
Y表示苯甲酰胺硫羰基或取代苯甲酰胺硫羰基、2-苯基-1,3,4-噻（噁）二唑-5-基或2-取代苯基-1,3,4-噻（噁）-5-基、苯甲（乙酮）亚胺基或取代苯甲（乙酮）亚胺基；在Y所涉及的苯环上的取代基主要为：H、卤素、硝基、氰基、CF3、C1-4烷基、甲氧基、C1-2羧酸基或羧酸酯基；取代基在苯环任意位置上的单取代或多取代，取代基相同或不同。
2.如权利要求1所述的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物，其特征在于，包括具有通式（I-1）结构的化合物：
其中：
X表示氧或NH；
R1表示氢；
R2表示H、卤素、硝基、甲氧基或C1-4烷基；
R3表示H、卤素、硝基、氰基、CF3、C1-4烷基或甲氧基，R2与R3位置可互换。
3.如权利要求1所述的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物，其特征在于，包括具有通式（I-2）结构的化合物：
其中：
X为氧或S；
R1表示氢；
R2表示H、卤素、硝基或C1-4烷基；
R3表示H、卤素、硝基、CF3、甲氧基或C1-4烷基，R2与R3位置可互换。
4.如权利要求1所述的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物，其特征在于，包括具有通式（I-3）结构的化合物：
其中：
R1表示氢或I；
R2表示H、硝基或卤素；
R3表示H、卤素、硝基、C1-4烷基或甲氧基，R2与R3位置可换；
R4为H或甲基。
5.权利要求2所述的通式（I-1）表示的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物的制备方法，其特征是使通式（II）表示的化合物与通式（III）表示的化合物反应：
通式（III）中R1、R2、R3、X的定义分别与通式（I-1）中R1、R2、R3、X的定义相同。
6.权利要求3所述的通式（I-2）表示的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物的制备方法，其特征是使通式（II）表示的化合物与通式（IV）表示的化合物反应：
通式（IV）中R1、R2、R3、X的定义分别与通式（I-2）中R1、R2、R3、X的定义相同。
7.权利要求4所述的通式（I-3）表示的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物的制备方法，其特征是使通式（II）表示的化合物与通式（V）表示的化合物反应：
通式（V）中R1、R2、R3、R4的定义分别与通式（I-3）中R1、R2、R3、R4的定义相同。
8.权利要求1所述的通式（I）表示的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物的应用，其特征在于：作为杀菌剂的有效成分。
9.权利要求1所述的通式（I）表示的2-甲基-4-氨基-5-(取代-1,2,3-三唑基)甲基嘧啶衍生物的应用，其特征在于：作为对小麦赤霉病菌、水稻纹枯病菌、黄瓜灰霉病菌、番茄早疫病菌、烟草赤星病菌和黄瓜炭疽病菌杀菌剂的有效成分。
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