CN103833672A - 一种n-丁基-5-苯基噻唑-4-甲酰胺类衍生物的制备方法 - Google Patents
一种n-丁基-5-苯基噻唑-4-甲酰胺类衍生物的制备方法 Download PDFInfo
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Abstract
本发明涉及有机化学领域,具体涉及一种N-丁基-5-苯基噻唑-4-甲酰胺类衍生物的制备方法。本发明以噻唑-4-甲酰胺衍生物和取代碘苯作为底物,以碘化亚铜为催化剂,氢氧化钠为碱,二氧六环为溶剂,在油浴120℃下,得到5-苯基-噻唑-4-甲酰胺衍生物;本发明合成方法具有收率高,原料易得,铜催化剂使用量少,不需要使用昂贵的有机碱试剂,反应设备简单,原子经济性高等诸多优点。
Description
技术领域
本发明涉及一种N-丁基-5-苯基噻唑-4-甲酰胺类衍生物的制备方法,属于有机化学合成方法学领域。
背景技术
在许多天然产物和合成活性物质中都存在着噻唑环结构,这类化合物展现出重要的生物活性,例如:抗菌活性、抗病毒活性、抗真菌活性等。其中5位苯基取代的噻唑环不仅仅存在于药物结构中还存在于许多有机功能材料中,例如:荧光染料、液晶等。传统噻唑环的合成方法是Hantzsch合成法,该方法只适用于合成简单的噻唑类化合物,对于取代噻唑的合成收率较低。因此过渡金属催化的偶联反应已经成为了构建取代噻唑的重要方法。
其中钯/铜催化的交叉脱氢偶联反应由于底物均不需要预活化,极大地实现原子经济性。目前报道的钯催化的噻唑环芳基化有:Tamba S.;Okubo Y.;Tanaka S et al.J.Org.Chem,2010,75:6998;Xie K.;Yang Z.;Zhou X et al.Org.Lett,2010,12,1564等。铜催化噻唑环芳基化的有:Zhao X.;Wu G.;Zhang Y et al.J.AM.CHEM.SOC,2011,133:3296;Huang G.;Sun H.;QiuX et al.Org.Lett,2011,13:5224等。这些方法都实现了取代噻唑的芳基化,但是钯催化反应使用的钯试剂较为昂贵,Pd催化反应在发生还原消除时还存在着β-H消除反应以及双键移位现象;而铜催化反应所使用的铜试剂使用量大,有机碱试剂昂贵,不易保存,条件苛刻。
本发明专利以N-丁基噻唑-4-甲酰胺衍生物和取代碘苯作为底物,以碘化亚铜为催化剂,氢氧化钠为碱,二氧六环为溶剂,在油浴120℃下,得到N-丁基-5-苯基-噻唑-4-甲酰胺衍生物;本发明合成方法具有收率高,原料易得,铜催化剂使用量少,不需要使用昂贵的有机碱试剂,反应设备简单,原子经济性高等诸多优点。
发明内容
本发明的目的是提供一种合成上述N-丁基-5-苯基噻唑-4-甲酰胺类衍生物的方法;
本发明的目的是通过以下技术方案来实现的,其特征在于通式I所示的:
通式I
其中,R1选自甲基、丙基、苯基或取代苯基;R1优选苯基、4-氯苯基、4-甲苯基、4-三氟甲基苯基;R2选自氢、卤素、甲基、硝基、甲氧基或三氟甲基;优选氢、甲氧基、甲基、溴。
N-丁基-5-苯基噻唑-4-甲酰胺类衍生物的制备方法(反应1),包括以下步骤:取一反应管,向其中加入N-丁基噻唑-4-甲酰胺类衍生物和取代碘苯,铜催化剂,碱和溶剂,加热反应12小时。所述铜催化剂包括CuI,CuBr,CuCl,Cu(CN),优选CuI;所述碱选自t-BuONa,t-BuOK,t-BuOLi,KOH,NaOH,Na2CO3,K2CO3,K3PO4,优选NaOH;所述溶剂选自二氧六环、甲苯、NMP、DMA、四氢呋喃、DMF,优选二氧六环。反应温度选自80℃-140℃,优选120℃。
反应1
参照反应1图解:
在反应管中加入N-丁基噻唑-4-甲酰胺类衍生物和取代碘苯,NaOH,CuI,dioxane,于120℃油浴中加热反应12小时,得到N-丁基-5-苯基噻唑-4-甲酰胺类衍生物。
具体实施方式
下面结合具体实施例来进一步描述本发明,本发明的优点和特点将会随着描述而更为清楚。但这些实施例仅是范例性的,并不对本发明的范围构成任何限制。本领域技术人员应该理解的是,在不偏离本发明的精神和范围下可以对本发明技术方案的细节和形式进行修改或替换,但这些修改和替换均落入本发明的保护范围内。
实施例1
N-丁基-2,5-苯基噻唑-4-甲酰胺(1)
取一反应管,加入N-丁基-2-苯基噻唑-4-甲酰胺(130mg,0.5mmol)和碘苯(153mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体155mg,产率92.3%。
IR:3046,3061,2950,2927,1669,1532,1476,1224,769,718,689cm-1;1H NMR(300MHz,CDCl3)δ7.94-7.96(m,2H),7.66-7.68(m,3H),7.41-7.48(m,6H),3.42(q,J=7.0Hz,2H),0.95(t,J=7.2Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ163.72,160.55,142.1,141.67,131.80,129.57,129.38,128.09,128.00,128.00,127.74,127.04,125.46,38.11,30.86,19.31,12.89ppm;MS(ESI)m/z337.06[M+H]+.mp:74-76℃.
实施例2
N-丁基-2-(4-氟苯基)-5-苯基噻唑-4-甲酰胺(2)
取一反应管,加入N-丁基-2-(4-氟苯基)噻唑-4-甲酰胺(139mg,0.5mmol)和碘苯(153mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体150mg,产率85%。
IR:3412,2957,2873,1679,1516,1474,1219,847,748,754,548cm-1;1H NMR(300MHz,CDCl3)δ7.91-7.96(m,2H),7.64-7.67(m,2H),7.58(br,1H),7.40-7.42(m,3H),7.14-7.19(m,2H),3.41(q,J=7.0Hz,2H),1.56-1.66(m,2H),0.95(t,J=7.2Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ164.78,162.49,161.45,160.44,142.09,141.66,129.35,128.06,127.67,127.47,127.36,127.06,115.34,115.05,38.13,30.86,19.30,12.89ppm;MS(ESI)m/z355.05[M+H]+.mp:114-115℃.
实施例3
N-丁基-2-(4-氯苯基)-5-苯基噻唑-4-甲酰胺(3)
取一反应管,加入N-丁基-2-(4-氯苯基)噻唑-4-甲酰胺(147mg,0.5mmol)和碘苯(153mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体163mg,产率88%。
IR:3268,2958,2928,2871,1643,1560,1500,1481,1104,837,754,690cm-1;1H NMR(300MHz,CDCl3)δ7.87-7.90(m,2H),7.64-7.67(m,2H),7.57(br,1H),7.40-7.46(m,5H),3.41(q,J=6.9Hz,2H),1.56-1.63(m,2H),0.95(t,J=7.3Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ162.31,160.38,142.38,141.77,135.53,130.24,129.35,129.17,128.31,128.12,127.08,126.63,38.14,30.86,19.31,12.90ppm;MS(ESI)m/z371.00[M+H]+.mp:118-119℃;.
实施例4
N-丁基-2-(4-溴苯基)-5-苯基噻唑-4-甲酰胺(4)
取一反应管,加入N-丁基-2-(4-溴苯基)噻唑-4-甲酰胺(169mg,0.5mmol)和碘苯(153mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体164mg,产率79%。
IR:3290,2949,2925,2866,1649,1534,1503,1002,831,753,707cm-1;1H NMR(300MHz,CDCl3)δ7.80-7.82(m,2H),7.59-7.66(m,5H),7.40-7.42(m,3H),3.41(q,J=6.9Hz,2H),1.56-1.67(m,2H),0.95(t,J=7.1Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ162.35,160.36,142.41,141.81,131.25,130.66,129.35,129.16,128.13,127.08,126.82,123.88,38.16,30.86,19.32,12.93ppm;MS(ESI)m/z414.95[M+H]+.mp:110-112℃.
实施例5
N-丁基-2-(4-甲基苯基)-5-苯基噻唑-4-甲酰胺(5)
取一反应管,加入N-丁基-2-(4-甲基苯基)噻唑-4-甲酰胺(137mg,0.5mmol)和碘苯(153mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体154mg,产率88%。
IR:3314,2956,2927,2858,1651,1536,1476,1256,836,753,690cm-1;1H NMR(300MHz,CDCl3)δ7.83(d,J=8.1Hz,2H),7.64-7.68(m,3H),7.40-7.42(m,3H),7.28(d,J=8.1Hz,2H),3.38-3.45(m,2H),2.42(s,3H),1.56-1.63(m,2H),1.35-1.44(m,2H),0.95(t,J=7.3Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ163.91,160.62,141.61,141.48,139.93,129.51,129.39,129.17,128.76,127.92,127.02,125.37,38.111,30.88,20.55,19.33,12.92ppm;MS(ESI)m/z351.07[M+H]+.mp:114-115℃.
实施例6
N-丁基-2-(4-三氟甲基甲苯基)-5-苯基噻唑-4-甲酰胺(6)
取一反应管,加入N-丁基-2-(4-三氟甲基苯基)噻唑-4-甲酰胺(164mg,0.5mmol)和碘苯(153mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体170mg,产率84%。
IR:34123,2963,2932,2862,1670,1536,1321,1160,846,777,691cm-1;1H NMR(300MHz,CDCl3)δ8.06(d,J=8.1Hz,2H),7.65-7.68(m,2H),7.57(br,1H),7.42-7.44(m,3H),3.39-3.46(m,2H),1.57-1.67(m,2H),1.38-1.48(m,2H)0.95(t,J=7.3Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ161.77,160.27,143.23,142.13,134.86,131.30,129.35,129.00,128.27,127.12,125.69,125.13,125.08,124.62,121.01,38.16,30.83,19.27,12.84ppm;MS(ESI)m/z405.04[M+H]+.mp:97-98℃.
实施例7
N-丁基-2-(4-甲氧基甲苯基)-5-苯基噻唑-4-甲酰胺(7)
取一反应管,加入N-丁基-2-(4-甲氧基苯基)噻唑-4-甲酰胺(145mg,0.5mmol)和碘苯(153mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体148mg,产率81%。
IR:3319,2961,2929,2857,1643,1574,1452,1258,837,761,688cm-1;1H NMR(300MHz,CDCl3)δ7.89(d,J=8.8Hz,2H),7.62-7.67(m,3H),7.38-7.43(m,3H),6.98(d,J=8.8Hz,2H),3.88(s,3H),3.41(q,J=6.8Hz,2H),1.58-1.66(m,2H),1.37-1.45(m,2H),0.95(t,J=7.3Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ163.63,160.64,160.55,141.38,141.13,129.55,129.36,127.85,126.99,126.97,124.69,113.39,54.47,38.08,30.87,19.31,12.89ppm;MS(ESI)m/z367.07[M+H]+.mp:99-100℃.
实施例8
N-丁基-2-甲基-5-苯基噻唑-4-甲酰胺(8)
取一反应管,加N-丁基-2-甲基噻唑-4-甲酰胺(99mg,0.5mmol)和碘苯(153mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到淡黄色液体108mg,产率79%。
IR:3263,2952,2920,2867,1646,1560,1508,1440,1239,756,708,635cm-1;1H NMR(300MHz,CDCl3)δ7.49-7.52(m,2H),7.29-7.38(m,4H),3.29(q,J=6.7Hz,2H),2.6(s,3H),1.44-1.51(m,2H),1.26-1.34(m,3H),0.85(t,J=7.3Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ162.53,161.00,142.27,141.03,130.07,129.76,128.21,127.43,38.48,31.27,19.72,18.47,13.30ppm;MS(ESI)m/z275.07[M+H]+.
实施例9
N-丁基-2-丙基-5-苯基噻唑-4-甲酰胺(9)
取一反应管,加N-丁基-2-丙基噻唑-4-甲酰胺(113mg,0.5mmol)和碘苯(153mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在1202油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到黄色液体118mg,产率78%。
IR:3049,2960,2871,2360,1671,1505,1463,1275,764,750,693cm-1;1H NMR(300MHz,CDCl3)δ7.58-7.60(m,2H),7.47(br,1H),7.37-7.38(m,3H),3.34-3.40(m,2H),2.90-2.96(m,2H),1.81-1.88(m,2H),1.55-1.64(m,2H),1.35-1.42(m,2H),1.04-1.08(m,3H),0.91-0.95(m,3H)ppm;13C NMR(75MHz,CDCl3)δ167.77,161.13,141.80,140.89,130.21,129.77,128.15,127.40,38.48,34.68,31.30,22.67,19.73,13.32,13.20ppm;MS(ESI)m/z303.09[M+H]+.
实施例10
N-丁基-5-(4-氟苯基)-2-苯基噻唑-4-甲酰胺(10)
取一反应管,加入N-丁基-2-苯基噻唑-4-甲酰胺(130mg,0.5mmol)和4-氟碘苯(167mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体140mg,产率79%。
IR:3413,2955,2929,2869,1656,1511,1227,830,766,693cm-1;1H NMR(300MHz,CDCl3)δ7.93-7.96(m,2H),7.63-7.68(m,3H),7.47-7.49(m,3H),7.11(t,J=8.7Hz,2H),3.41(q,J=7.0Hz,2H),1.56-1.66(m,3H),1.38-1.47(m,3H),0.95(t,J=7.3Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ163.81,163.72,160.50,141.66,140.92,131.66,131.38,129.70,128.11,125.45,114.23,113.94,38.12,30.84,19.30,12.87ppm;MS(ESI)m/z355.06[M+H]+.mp:85-86℃.
实施例11
N-丁基-5-(4-氯苯基)-2-苯基噻唑-4-甲酰胺(11)
取一反应管,加入N-丁基-2-苯基噻唑-4-甲酰胺(130mg,0.5mmol)和4-氯碘苯(179mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体141mg,产率76%。
IR:3410,2951,2927,2869,1648,1533,1499,1091,827,763,688cm-1;1H NMR(300MHz,CDCl3)δ7.92-7.95(m,2H),7.59-7.64(m,3H),7.47-7.49(m,3H),7.39(d,J=7.7Hz,2H),3.41(q,J=6.5Hz,2H),1.56-1.66(m,2H),1.38-1.47(m,2H),0.95(t,J=7.3Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ163.97,160.42,141.86,140.62,134.10,131.60,130.72,129.75,128.13,127.87,125.47,38.13,30.84,19.30,12.89ppm;MS(ESI)m/z371.01[M+H]+.mp:102-104℃.
实施例12
N-丁基-5-(4-溴苯基)-2-苯基噻唑-4-甲酰胺(12)
取一反应管,加入N-丁基-2-苯基噻唑-4-甲酰胺(130mg,0.5mmol)和4-溴碘苯(212mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体166mg,产率80%。
IR:3410,2957,2928,2869,1671,1533,1439,1072,825,765,690cm-1;1H NMR(300MHz,CDCl3)δ7.82-7.83(m,2H),7.54(br,1H),7.25-7.43(m,7H),3.27-3.34(m,2H),1.46-1.53(m,2H),1.27-1.35(m,2H),0.83-0.88(m,3H)ppm;13C NMR(75MHz,CDCl3)δ165.00,161.38,142.88,141.59,132.59,131.95,131.18,130.73,129.35,129.12,126.47,123.42,39.13,31.83,20.28,13.87ppm;MS(ESI)m/z414.96[M+H]+.mp:107-108℃.
实施例13
N-丁基-5-(4-甲基苯基)-2-苯基噻唑-4-甲酰胺(13)
取一反应管,加入N-丁基-2-苯基噻唑-4-甲酰胺(130mg,0.5mmol)和4-甲基碘苯(164mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体149mg,产率85%。
IR:3345,2953,2931,2869,1652,1508,1477,812,762,689cm-1;1H NMR(300MHz,CDCl3)δ7.92-7.95(m,2H),7.61(br,1H),7.57(d,J=7.9Hz,2H),7.44-7.47(m,3H),7.23(d,J=7.9Hz,2H),3.40(q,J=7.0Hz,2H),2.38(s,3H),1.55-1.62(m,2H),1.37-1.44(m,2H),0.94(t,J=7.3Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ163.36,160.61,142.36,141.50,138.07,131.86,129.50,129.27,128.07,127.78,126.43,125.43,38.10,30.89,20.45,19.33,12.92ppm;MS(ESI)m/z351.07[M+H]+.mp:89-90℃.
实施例14
N-丁基-5-(4-甲氧基苯基)-2-苯基噻唑-4-甲酰胺(14)
取一反应管,加入N-丁基-2-苯基噻唑-4-甲酰胺(130mg,0.5mmol)和4-甲氧基碘苯(176mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体161mg,产率88%。
IR:3373,2955,2928,2855,1664,1604,1508,1248,1186,832,763,686cm-1;1H NMR(300MHz,CDCl3)δ7.93-7.95(m,2H),7.62-7.65(m,3H),7.45-7.47(m,3H),6.93-6.96(m,2H),3.84(s,3H),3.38-3.45(m,2H),1.56-1.64(m,2H),1.38-1.45(m,2H),0.93-0.98(m,3H)ppm;13C NMR(75MHz,CDCl3)δ162.95,160.71,159.24,142.31,141.06,131.85,130.79,129.45,128.05,125.38,121.54,112.49,54.33,38.10,30.89,19.32,12.92ppm;MS(ESI)m/z367.07[M+H]+.mp:77-78℃.
实施例15
N-丁基-5-(4-硝基苯基)-2-苯基噻唑-4-甲酰胺(15)
取一反应管,加入N-丁基-2-苯基噻唑-4-甲酰胺(130mg,0.5mmol)和4-硝基碘苯(187mg,0.75mmol,1.5eq),碘化亚铜(19mg,0.1mmol,0.2eq),NaOH(40mmg,1mmol,2eq),二氧六环2mL,在120℃油浴中反应12个小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经过水、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体80mg,产率42%。
IR:3388,2950,2868,1676,1593,1508,1345,853,750,691cm-1;1H NMR(300MHz,CDCl3)δ8.20(d,J=8.7Hz,2H),7.87-7.90(m,2H),7.77(d,J=8.7Hz,2H),7.60(br,1H),7.44-7.45(m,3H),3.31-3.38(m,2H),1.50-1.57(m,2H),1.31-1.39(m,2H),0.88(t,J=7.2Hz,3H)ppm;13C NMR(75MHz,CDCl3)δ165.28,160.12,146.79,142.88,138.73,136.31,131.30,130.43,130.13,128.23,125.59,122.14,38.19,30.76,19.25,12.82ppm;MS(ESI)m/z382.01[M+H]+.mp:148-150℃。
Claims (5)
2.权利要求1所述的方法,其特征在于所述的铜催化剂包括CuI,CuBr,CuCl,Cu(CN);优选CuI。
3.权利要求1所述的方法,其特征在于所述的碱选自t-BuONa,t-BuOK,t-BuOLi,KOH,NaOH,Na2CO3,K2COa,K3PO4;优选NaOH。
4.权利要求1所述的方法,其特征在于所述的溶剂选自二氧六环,甲苯,NMP,DMA,四氢呋喃,DMF;优选二氧六环。
5.权利要求1所述的方法,其特征在于反应温度选自8O℃-140℃,优选120℃。
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018500286A (ja) * | 2014-10-30 | 2018-01-11 | ヤンセン ファーマシューティカ エヌ.ベー. | RORγtのモジュレーターとしてのアミド置換チアゾール |
US10975057B2 (en) | 2018-06-18 | 2021-04-13 | Janssen Pharmaceutica Nv | 6-aminopyridin-3-yl pyrazoles as modulators of RORgT |
US10975037B2 (en) | 2018-06-18 | 2021-04-13 | Janssen Pharmaceutica Nv | Phenyl substituted pyrazoles as modulators of RORγt |
US10975068B2 (en) | 2016-04-27 | 2021-04-13 | Janssen Pharmaceutica Nv | 6-aminopyridin-3-yl thiazoles as modulators of RORγT |
US11034658B2 (en) | 2018-06-18 | 2021-06-15 | Janssen Pharmaceutica Nv | Pyridinyl pyrazoles as modulators of RORγT |
US11345666B2 (en) | 2018-06-18 | 2022-05-31 | Janssen Pharmaceutica Nv | Phenyl and pyridinyl substituted imidazoles as modulators of RORγT |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102120733A (zh) * | 2010-01-07 | 2011-07-13 | 药源药物化学(上海)有限公司 | 一种非布索坦的制备方法 |
CN102174028A (zh) * | 2011-03-17 | 2011-09-07 | 中国药科大学 | 一种噻唑-4-甲酸乙酯类衍生物的制备方法 |
WO2012091115A1 (ja) * | 2010-12-29 | 2012-07-05 | キッセイ薬品工業株式会社 | アセチレン誘導体及びその医薬用途 |
-
2014
- 2014-03-28 CN CN201410120640.6A patent/CN103833672A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102120733A (zh) * | 2010-01-07 | 2011-07-13 | 药源药物化学(上海)有限公司 | 一种非布索坦的制备方法 |
WO2012091115A1 (ja) * | 2010-12-29 | 2012-07-05 | キッセイ薬品工業株式会社 | アセチレン誘導体及びその医薬用途 |
CN102174028A (zh) * | 2011-03-17 | 2011-09-07 | 中国药科大学 | 一种噻唑-4-甲酸乙酯类衍生物的制备方法 |
Non-Patent Citations (2)
Title |
---|
SOMMAI PIVSA-ART,等: "Palladium-Catalyzed Arylation of Azole Compounds with Aryl Halides in the Presence of Alkali Metal Carbonates and the Use of Copper Iodide in the Reaction", 《BULL. CHEM. SOC. JPN.》, vol. 71, no. 2, 31 December 1998 (1998-12-31), pages 468 - 469 * |
陶传洲: "铜催化的乌尔曼缩合反应的研究", 《中国科学技术大学博士论文》, 30 June 2009 (2009-06-30), pages 96 - 111 * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018500286A (ja) * | 2014-10-30 | 2018-01-11 | ヤンセン ファーマシューティカ エヌ.ベー. | RORγtのモジュレーターとしてのアミド置換チアゾール |
CN108064224A (zh) * | 2014-10-30 | 2018-05-22 | 詹森药业有限公司 | 作为Rorγt的调节剂的酰胺取代的噻唑 |
CN108064224B (zh) * | 2014-10-30 | 2022-03-29 | 詹森药业有限公司 | 作为Rorγt的调节剂的酰胺取代的噻唑 |
US10975068B2 (en) | 2016-04-27 | 2021-04-13 | Janssen Pharmaceutica Nv | 6-aminopyridin-3-yl thiazoles as modulators of RORγT |
US10975057B2 (en) | 2018-06-18 | 2021-04-13 | Janssen Pharmaceutica Nv | 6-aminopyridin-3-yl pyrazoles as modulators of RORgT |
US10975037B2 (en) | 2018-06-18 | 2021-04-13 | Janssen Pharmaceutica Nv | Phenyl substituted pyrazoles as modulators of RORγt |
US11034658B2 (en) | 2018-06-18 | 2021-06-15 | Janssen Pharmaceutica Nv | Pyridinyl pyrazoles as modulators of RORγT |
US11345666B2 (en) | 2018-06-18 | 2022-05-31 | Janssen Pharmaceutica Nv | Phenyl and pyridinyl substituted imidazoles as modulators of RORγT |
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