一种1,2,3,4-四氢异喹啉衍生物的制备方法转让专利
申请号 : CN201810659587.5
文献号 : CN108997215B
文献日 : 2020-05-22
发明人 : 周强辉 , 钱光印 , 白淼
申请人 : 武汉大学
摘要 :
权利要求 :
1.一种如式I所示的1,2,3,4-四氢异喹啉衍生物的制备方法,其特征在于,所述方法为:在氩气保护下,以式A所示的芳基碘化物、式B所示的氮杂环丙烷化合物和式C所示的烯烃化合物为起始原料,在催化剂D、配体E、降冰片烯衍生物G、碱F的作用下,在30℃到120℃下于有机溶剂H中搅拌反应48小时以内,反应结束后反应混合物经抽滤、浓缩和纯化制得如式I所示的1,2,3,4-四氢异喹啉衍生物;式A所示的芳基碘化物:式B所示的氮杂环丙烷化合物:式C所示的烯烃化合物:催化剂D:配体E:碱F:降冰片烯衍生物G的投料摩尔比为(1-10):
1:(1-10):(0.05-1):(0.1-1):(1-10):(0.05-3);
所述反应的反应式如下式所示:
式I及式A所示的芳基碘化物、式B所示的氮杂环丙烷化合物和式C所示的烯烃化合物中R1、R2和R3分别为氢、芳基、杂环芳基、烷基、取代烷基、酯基、酰胺基、氰基、硝基、磺酰基、烷氧基、烷硫基和卤素中的任意一种,为相同或为不同;R4和R5分别为氢、酯基、酰胺基中的任
1 2
意一种,为相同或为不同;其中m表示R的个数,0≤m≤4;n表示R的个数,0≤n≤4;
上述芳基带有一个或多个取代基,为芳基、杂环芳基、烷基、酯基、氰基、硝基、酰胺基、磺酰基、烷氧基和卤素中的任意一种,所述芳基上带有取代基中的一种或2种及2种以上,当具有2种及2种以上取代基时,取代基可以相同或不同;
上述烷基是指具有1~20个碳原子的烷基;
上述取代烷基表示为 其中o为0和任意整数,X可以为OR6、OSi(R6)3、SR6、SSi(R6)3、SeR6、N(R6)2、Si(R6)3,其中R6代表氢、芳基、杂环芳基、烷基、酯基、氰基、硝基、酰胺基、磺酰基、卤素,且是这些取代基中的一种或2种及2种以上,当具有2种及2种以上取代基时,这多个取代基为相同或不同;
上述烷氧基是指具有1~10个碳原子的烷氧基;
所述催化剂D使用钯催化剂来促进反应,采用的钯催化剂为Pd(OAc)2;
所述配体E采用膦配体三(呋喃-2-基)膦;
所述碱F采用碳酸钾;
所述降冰片烯衍生物G为2-对甲苯基-3a,4,7,7a-四氢-1H-4,7-亚甲异吲哚-1,3(2H)-二酮;
所述的溶剂H为乙腈。
2.根据权利要求1所述的制备方法,其特征在于,芳基碘化物A:氮杂环丙烷B:烯烃C:催化剂D:配体E:碱F:降冰片烯衍生物G的投料摩尔比为1.2:1:1.5:0.1:0.24:2.0:0.2。
3.根据权利要求1所述的制备方法,其特征在于,制备方法中加热过程可采用油浴,为硅油或石蜡油。
4.根据权利要求1所述的制备方法,其特征在于,所述抽滤过程使用砂芯漏斗,在减压的条件下过滤。
5.根据权利要求1所述的制备方法,其特征在于,所述浓缩过程可采用常压蒸馏、用旋转蒸发仪减压浓缩。
6.根据权利要求1所述的制备方法,其特征在于,所述纯化过程是通过柱层析得到纯净的产物。
说明书 :
一种1,2,3,4-四氢异喹啉衍生物的制备方法
技术领域
背景技术
Chem.Rev.2002,102,1669.[3]V.G.Kartsev,Med.Chem.Res.2004,13,325.[4]
K.W.Bentley,Nat.Prod.Rep.2006,23,444.[5]N.Cabedo,I.Berenguer,B.Figadere,D.Cortes,Curr.Med.Chem.2009,16,2441.[6]P.Zhu,W.Ye,J.Li,Y.Zhang,W.Huang,M.Cheng,Y.Wang,Y.Zhang,H.Liu,J.Zuo,Chem.Biol.Drug Des.2017,89,443.[7]
K.Fujimoto,T.Oka,M.Morimoto,Cancer Res.1987,47,1516.[8]R.Kanamaru,Y.Konishi,C.Ishioka,H.Kakuta,T.Sato,A.Ishikawa,M.Asamura,A.Wakui,Cancer
Chemother.Pharmacol.1988,22,197.[9]L.Goldman MD,A.I.Schafer MD,2011,Goldman's Cecil Medicine(24th ed.).Philadelphia:Elsevier Saunders.ISBN 1437727883.[10]M.F.Roberts,M.Wink,1998,Alkaloids.New York:Plenum Press.ISBN 0-306-45465-3.[11]Z.Yao,X.Wei,X.Wu,J.L.Katz,T.Kopajtic,N.H.Greig,H.Sun,Eur.J.Med.Chem.2011,
46,1841.[12]T.Eicher,S.Hauptmann and A.Speicher,The Chemistry of
Heterocycles:Structures,Reactions,Synthesis,and Applications,John Wiley&Sons,
2013.[13]A.R.Katritzky,C.A.Ramsden,J.A.Joule and V.V.Zhdankin,Handbook of heterocyclic chemistry,Elsevier,2010.)。
2005,339.[7]J. A.P.Antonchick,F.Wu,H.Waldmann,Angew.Chem.Int.Ed.2011,
50,8538.);(3)过渡金属催化氢化反应([1]J.-H.Xie,P.-C.Yan,Q.-Q.Zhang,K.-X.Yuan,Q.-L.Zhou,ACS Catal.2012,2,561.[2]F.Berhal,Z.Wu,Z.Zhang,T.Ayad,
V.Ratovelomanana-Vidal,Org.Lett.2012,14,3308.);(4)3,4-二氢异喹啉的亲核加成反应(B.A.Granger,K.Kaneda,S.F.Martin,Org.Lett.2011,13,4542.);(5)分子内Heck反应(A.Endo,A.Yanagisawa,M.Abe,S.Tohma,T.Kan,T.Fukuyama,J.Am.Chem.Soc.2002,124,
6552.);(4)亲电诱导的环化反应(T.Wirth,G.Fragale,Synthesis 1998,162.)。然而,这些方法大多需要预先合成特殊的官能团,极大地限制了这些方法的使用范围。因此发展高效、简洁的新的合成方法显得尤为重要。
发明内容
10):(0.05-1):(0.1-1):(1-10):(0.05-3),优选为芳基碘化物A:氮杂环丙烷B:烯烃C:催化剂D:配体E:碱F:降冰片烯衍生物G=1.2:1:1.5:0.1:0.24:2.0:0.2;
合物中R、R、R、R、和R彼此独立地为氢、芳基、杂环芳基、烷基、取代烷基、酯基、酰胺基、氰基、硝基、磺酰基、烷氧基、烷硫基和卤素中的任意一种,为相同或不同;其中m表示R1的个数,0≤m≤4;n表示R2的个数,0≤n≤4;
基,q代表取代基个数,0≤q≤2;R的构型可以是内型(Endo)或外型(Exo)或两者的混合物:
具体实施方式
2.7Hz,2H),3.80–3.73(m,1H),3.69–3.62(m,1H),2.78–2.66(m,3H),2.60(dd,J=14.6,
3.9Hz,1H),2.35(s,3H),2.31(s,3H),1.28(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3):δ
170.25,143.25,137.25,134.07,133.93,133.11,129.39,128.73,127.18,127.15,126.95,
61.14,51.52,41.03,39.10,26.54,21.56,18.81,14.29.HRMS(ESI-TOF):理论计算值:
C21H25NaNSO4[M+Na+]410.1397,实测值:410.1410。
1.24(m,6H).13C NMR(100MHz,CDCl3):δ170.23,143.22,139.98,137.28,133.52,133.15,
129.40,127.42,127.28,126.85,126.81,61.13,51.09,42.01,39.10,26.77,24.43,21.56,
15.33,14.29.HRMS(ESI-TOF):理论计算值:C22H27NaNSO4[M+Na+]424.1553,实测值:
424.1556。
2H),3.76–3.67(m,2H),3.23–3.17(m,1H),2.80(dd,J=14.6,10.2Hz,1H),2.73–2.69(m,
2H),2.55(dd,J=14.6,3.9Hz,1H),2.31(s,3H),1.30–1.24(m,6H),1.22(d,J=6.7Hz,3H).13C NMR(100MHz,CDCl3):δ170.13,144.97,143.19,137.34,133.00,132.57,129.38,
127.57,127.27,126.79,124.01,61.12,50.97,42.49,38.98,27.90,26.87,25.26,23.49,
21.54,14.29.HRMS(ESI-TOF):理论计算值:C23H29NaNSO4[M+Na+]438.1710,实测值:
438.1712。
合物I-4(无色油状液体,产率71%)。H NMR(400MHz,CDCl3):δ7.61–7.57(m,2H),7.51–7.48(m,2H),7.44–7.40(m,2H),7.36–7.32(m,1H),7.08–7.02(m,3H),6.72(d,J=8.1Hz,1H),
6.54–6.52(m,1H),5.83(dd,J=10.2,3.7Hz,1H),5.15(s,2H),4.12–3.99(m,2H),3.94–
3.88(m,1H),3.57–3.49(m,1H),2.97(dd,J=14.2,3.7Hz,1H),2.72–2.64(m,2H),2.57–
2.51(m,1H),2.31(s,3H),1.22(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3):δ169.81,
153.62,142.43,137.09,136.23,133.86,128.63,128.06,127.33,127.10,126.56,126.32,
123.75,120.98,108.55,69.23,60.14,49.01,39.61,37.83,25.35,20.89,13.58.HRMS(ESI-TOF):理论计算值:C27H29NaNSO5[M+Na+]502.1659,实测值:502.1661。
3.71–3.63(m,1H),2.85–2.64(m,4H),2.29(s,3H),1.29(t,J=7.1Hz,3H),0.96(s,9H),
0.17(d,J=5.3Hz,6H).13C NMR(100MHz,CDCl3):δ170.15,143.12,137.32,136.65,133.53,
132.98,129.27,128.51,127.30,127.23,126.62,62.70,61.08,50.85,41.80,38.64,
26.21,26.13,21.54,18.60,14.32,-5.15,-5.23.HRMS(ESI-TOF):理论计算值:
+
C27H39NaSiNSO5[M+Na]540.2210,实测值:540.2213。
得化合物I-6(无色油状液体,产率85%)。H NMR(400MHz,CDCl3):δ7.58–7.56(m,2H),7.09(d,J=8.0Hz,2H),6.91(d,J=7.7Hz,1H),6.67(d,J=7.7Hz,1H),5.68(dd,J=10.1,
3.8Hz,1H),4.13(qd,J=7.2,3.2Hz,2H),3.78–3.72(m,1H),3.64–3.57(m,1H),2.76–2.55(m,4H),2.31(s,3H),2.23(s,3H),2.21(s,3H),1.27(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3):δ170.24,143.11,137.36,135.19,133.80,132.21,130.55,129.31,128.76,
127.15,126.45,61.03,51.77,41.18,38.89,26.51,21.50,20.52,14.74,14.24.HRMS(ESI-TOF):理论计算值:C22H27NaNSO4[M+Na+]424.1553,实测值:424.1555。
10.1Hz,1H),2.67–2.55(m,3H),2.32(s,3H),2.25(d,J=2.3Hz,3H),1.27(t,J=7.2Hz,
3H).19F NMR(377MHz,CDCl3)δ-117.89.13C NMR(100MHz,CDCl3):169.81,159.58(d,J=
242.9Hz),143.28,137.02,135.61(d,J=3.5Hz),129.30,128.33(d,J=3.2Hz),127.60(d,J=8.4Hz),127.05,120.77(d,J=16.5Hz),113.89(d,J=23.3Hz),61.10,51.25(d,J=
3.1Hz),40.77,38.67,25.85,21.44,14.13,10.07(d,J=5.9Hz).HRMS(ESI-TOF):理论计算值:C21H24FNaNSO4[M+Na+]428.1302,实测值:428.1302。
7.2,2.6Hz,2H),3.85–3.78(m,1H),3.63–3.55(m,1H),2.74–2.54(m,4H),2.38(s,3H),2.33
13
(s,3H),1.27(t,J=7.1Hz,3H). CNMR(100MHz,CDCl3):δ169.89,143.47,137.13,135.69,
133.09,131.91,131.73,129.46,128.03,127.90,127.18,61.25,51.85,40.80,38.43,
26.20,21.58,15.67,14.27.HRMS(ESI-TOF):理论计算值:C21H24ClNaNSO4[M+Na+]444.1007,实测值:444.1007。
2.63(m,3H),2.55(dd,J=14.7,3.9Hz,1H),2.33(s,3H),2.32(s,3H),1.26(t,J=7.2Hz,
3H).19F NMR(377MHz,CDCl3)δ-116.08.13C NMR(100MHz,CDCl3)δ170.00,161.35(d,J=
245.6Hz),143.42,137.14,136.47(d,J=8.1Hz),135.39(d,J=8.1Hz),129.85(d,J=
3.0Hz),129.42,127.13,115.53(d,J=21.2Hz),113.21(d,J=20.9Hz)61.15,51.15,
40.94,38.58,26.65(d,J=1.7Hz),21.54,18.86(d,J=1.7Hz),14.26.HRMS(ESI-TOF):理论计算值:C21H24FNaNSO4[M+Na+]428.1302,实测值:428.1306。
129.47,127.11,120.81,61.22,51.19,40.66,38.59,26.26,21.59,18.57,14.26.HRMS(ESI-TOF):理论计算值:C21H24BrNaNSO4[M+Na+]488.0502,实测值:488.0507。
1H),4.14(qd,J=7.2,3.1Hz,2H),3.87(s,3H),3.83–3.79(m,1H),3.68–3.61(m,1H),2.76–
2.69(m,3H),2.58(dd,J=14.7,3.9Hz,1H),2.40(s,3H),2.31(s,3H),1.27(t,J=7.1Hz,
3H).13C NMR(100MHz,CDCl3):δ169.86,166.93,143.53,139.06,137.10,134.41,133.51,
129.65,129.50,128.78,128.23,127.12,61.30,52.29,51.51,40.53,38.73,26.45,21.58,
18.83,14.29.HRMS(ESI-TOF):理论计算值:C23H27NaNSO6[M+Na+]468.1451,实测值:
468.1460。
(无色油状液体,产率84%)。H NMR(400MHz,CDCl3):δ8.08(d,J=8.5Hz,1H),7.79(dd,J=
8.2,1.3Hz,1H),7.62–7.53(m,4H),7.50–7.46(m,1H),6.96(dd,J=10.7,8.2Hz,3H),6.22(dd,J=10.2,3.4Hz,1H),4.25–4.17(m,2H),4.07–4.01(m,1H),3.71–3.63(m,1H),2.94–
2.65(m,4H),2.25(s,3H),1.33(t,J=7.1Hz,3H).13C NMR(100MHz,CDCl3):δ170.47,
143.21,137.57,132.52,130.67,130.05,129.58,129.31,128.99,127.80,127.31,127.15,
127.14,125.54,122.10,61.26,51.13,41.33,38.17,26.81,21.48,14.33.HRMS(ESI-TOF):
理论计算值:C24H25NaNSO4[M+Na+]446.1396,实测值:446.1398。
7.29(s,1H),6.99(d,J=8.0Hz,2H),6.17(dd,J=9.9,3.7Hz,1H),4.23–4.16(m,2H),4.07–
4.01(m,1H),3.68–3.60(m,1H),2.89–2.73(m,3H),2.68–2.62(m,1H),2.27(s,3H),1.32(t,J=7.1Hz,3H).13C NMR(100MHz,CDCl3):δ170.19,143.51,137.30,131.58,131.08,130.90,
130.81,130.26,129.38,128.25,128.03,127.10,126.92,122.53,122.42,61.34,50.90,
41.14,37.85,26.43,21.51,14.31.HRMS(ESI-TOF):理论计算值:C24H24BrNaNSO4[M+Na+]
524.0502,实测值:524.0507。
4.14–4.10(m,2H),3.89–3.84(m,1H),3.57–3.49(m,1H),2.85(dd,J=14.5,3.9Hz,1H),
2.66–2.57(m,2H),2.53–2.46(m,1H),2.34(s,3H),1.27(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3):δ169.76,147.22,143.44,143.29,137.26,129.44,128.08,127.29,126.20,
111.71,107.63,101.84,61.16,51.17,40.38,38.40,26.17,21.62,14.29.HRMS(ESI-TOF):
理论计算值:C21H22NaClNSO6[M+Na+]474.0749,实测值:474.0749。
1H),7.64–7.61(m,2H),7.14(d,J=8.0Hz,2H),6.45(d,J=5.3Hz,1H),5.57(dd,J=9.8,
3.9Hz,1H),4.13–4.04(m,2H),3.97(s,3H),3.97–3.92(m,1H),3.50–3.42(m,1H),2.90(dd,J=14.5,3.9Hz,1H),2.69–2.58(m,2H),2.51–2.45(m,1H),2.34(s,3H),1.25(t,J=7.2Hz,
3H).13C NMR(100MHz,CDCl3):δ170.29,159.87,144.64,144.31,143.49,137.62,129.52,
127.26,118.61,117.68,60.97,53.73,49.03,39.38,37.81,25.73,21.60,14.29.HRMS+
(ESI-TOF):理论计算值:C20H24NaN2SO5[M+Na]427.1298,实测值:427.1298。
1H),3.79–3.73(m,1H),3.69(s,3H),3.66–3.61(m,1H),2.79–2.59(m,4H),2.34(s,3H),
2.32(s,3H).13C NMR(100MHz,CDCl3):δ170.62,143.29,137.18,133.96,133.90,133.13,
129.42,128.77,127.20,127.17,126.96,52.17,51.53,40.86,39.19,26.66,21.57,+
18.80.HRMS(ESI-TOF):理论计算值:C20H23NaNSO4[M+Na]396.1240,实测值:396.1237。
2H),7.05–7.03(m,2H),6.98–6.93(m,2H),6.67(dd,J=7.0,1.9Hz,1H),5.63–5.57(m,1H),
3.83–3.77(m,1H),3.69–3.61(m,1H),2.68–2.51(m,4H),2.34(s,3H),2.28(s,3H),1.49(s,
13
9H). C NMR(100MHz,CDCl3):δ169.42,143.11,137.32,134.13,133.88,132.85,129.26,
128.52,127.13,126.96,126.89,81.41,51.57,42.01,38.65,28.11,25.97,21.52,
18.76.HRMS(ESI-TOF):理论计算值:C23H29NaNSO4[M+Na+]438.1710,实测值:438.1715。
5.16–5.06(m,2H),3.78–3.72(m,1H),3.69–3.62(m,1H),2.81(dd,J=14.6,10.0Hz,1H),
2.72–2.63(m,3H),2.32(s,3H),2.31(s,3H).13C NMR(100MHz,CDCl3):δ170.10,143.29,
137.13,135.88,133.99,133.93,133.19,129.43,128.78,128.64,128.59,128.34,127.21,
126.93,67.01,51.54,41.08,39.31,26.68,21.58,18.84.HRMS(ESI-TOF):理论计算值:
C26H27NaNSO4[M+Na+]472.1553,实测值:472.1557。
1H),2.76–2.72(m,2H),2.63(dd,J=14.3,4.1Hz,1H),2.34(s,3H),2.30(s,3H).13C NMR(100MHz,CDCl3):δ170.54,143.05,137.25,134.67,133.98,133.30,129.31,128.66,
127.16,127.00,126.84,61.51,51.07,39.56,38.79,32.22,26.86,21.52,18.68.HRMS(ESI-TOF):理论计算值:C21H26NaN2SO4[M+Na+]425.1505,实测值:425.1507。
2H),7.01–6.93(m,2H),6.76–6.74(m,1H),5.60(dd,J=9.3,3.7Hz,1H),3.75–3.60(m,2H),
2.91(dd,J=15.3,9.4Hz,1H),2.72–2.69(m,2H),2.62–2.44(m,3H),2.31(s,3H),2.31(s,
3H),1.06(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3):δ207.96,143.38,136.73,134.61,
133.82,133.09,129.42,128.80,127.27,127.02,126.87,50.80,48.55,39.48,36.41,
26.77,21.58,18.90,7.63.HRMS(ESI-TOF):理论计算值:C21H25NaNSO3[M+Na+]472.1553,实测值:472.1557。
3.66–3.59(m,1H),2.92(dd,J=15.5,9.2Hz,1H),2.77–2.66(m,2H),2.58–2.41(m,3H),
2.32(s,3H),2.30(s,3H),1.57–1.49(m,1H),1.48–1.40(m,2H),0.89(s,3H),0.87(s,3H).13C NMR(100MHz,CDCl3):δ207.68,143.32,136.81,134.69,133.83,133.12,129.40,
128.79,127.27,127.00,126.87,50.61,48.76,41.27,39.50,32.34,27.71,26.85,22.53,
21.57,18.92.HRMS(ESI-TOF):理论计算值:C24H31NaNSO3[M+Na+]436.1917,实测值:
436.1925。
14.3,6.8Hz,1H),5.58(dd,J=10.0,3.7Hz,1H),4.30–4.22(m,3H),4.00(dd,J=6.8,
2.0Hz,1H),3.97–3.88(m,2H),3.78–3.69(m,2H),2.82–2.79(m,1H),2.74(t,J=7.3Hz,
2H),2.66(dd,J=14.7,3.8Hz,1H),2.33(s,3H),2.31(s,3H).13C NMR(100MHz,Acetone-d6):δ170.44,152.62,144.05,138.44,134.91,134.50,134.21,130.19,129.22,127.85,
127.81,127.63,87.18,66.71,63.65,52.29,41.11,39.78,26.95,21.28,18.67.HRMS(ESI-TOF):理论计算值:C23H27NaNSO5[M+Na+]452.1502,实测值:452.1505。
3H),7.47–7.42(m,2H),7.07–7.02(m,3H),6.98–6.95(m,1H),6.85(d,J=7.4Hz,1H),5.83(dd,J=8.2,4.2Hz,1H),3.70–3.66(m,2H),3.60(dd,J=15.9,8.2Hz,1H),3.03(dd,J=
15.9,4.3Hz,1H),2.91–2.78(m,2H),2.28(s,3H),2.28(s,3H).13C NMR(100MHz,CDCl3):δ
196.52,143.16,136.88,136.85,135.03,134.09,133.51,133.33,129.38,128.88,128.73,
128.36,127.28,127.10,126.87,50.61,44.82,39.96,27.46,21.55,19.12.HRMS(ESI-TOF):理论计算值:C25H25NaNSO3[M+Na+]442.1447,实测值:442.1450。
7.43–7.39(m,1H),7.32–7.27(m,2H),7.01–6.94(m,2H),6.73(dd,J=7.3,1.7Hz,1H),5.61(dd,J=10.2,3.8Hz,1H),4.17–4.11(m,2H),3.84–3.78(m,1H),3.71–3.63(m,1H),2.75(dd,J=14.7,10.2Hz,1H),2.68–2.58(m,3H),2.35(s,3H),1.28(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3):δ170.11,140.18,133.81,132.89,132.48,128.74,128.68,127.19,
127.04,126.94,61.09,51.55,40.83,39.00,26.38,18.73,14.26.HRMS(ESI-TOF):理论计+
算值:C20H23NaNSO4[M+Na]396.1240,实测值:396.1248.
1H),4.18–4.13(m,2H),3.90–3.85(m,1H),3.75–3.68(m,1H),2.80–2.69(m,3H),2.63(dd,J=15.0,3.8Hz,1H),2.36(s,3H),1.29(t,J=7.1Hz,3H).13C NMR(100MHz,CDCl3):δ169.94,
149.84,146.16,133.89,132.37,130.10,129.00,128.33,127.68,127.15,123.98,61.33,
51.92,40.45,39.12,26.38,18.77,14.31.HRMS(ESI-TOF):理论计算值:C20H22NaN2SO6[M+Na+]441.1091,实测值:441.1092。
反应容器冷却至室温后,用水(5mL)淬灭,用乙酸乙酯(3×5mL)萃取,Na2SO4干燥,过滤,真空下浓缩。用柱色谱纯化,洗脱剂为石油醚:乙酸乙酯=10:1(v/v),得到化合物I-26(白色固体,产率63%)。熔点:131–133℃.1H NMR(400MHz,CDCl3):δ9.47(dd,J=3.1,2.1Hz,1H),
7.56–7.54(m,2H),7.42–7.33(m,3H),6.49(t,J=1.0Hz,1H),5.16(d,J=10.2Hz,1H),5.02(d,J=10.2Hz,1H),3.27(dd,J=15.9,2.2Hz,1H),2.77(t,J=6.2Hz,2H),2.50(dd,J=
15.9,3.1Hz,1H),1.82–1.70(m,8H),1.66–1.60(m,2H),1.41(s,3H);13C NMR(100MHz,CDCl3):δ203.6,160.7,158.9,155.1,149.0,136.4,129.9,128.7(2C),128.5,112.4,
105.3,105.1,54.3,39.7,35.9,32.7,28.3,26.1,25.2,18.8;HRMS(ESI-TOF):理论计算值:
C24H26NaO5[M+Na+]417.1672,实测值:417.1670。
7.7Hz,1H),5.73–5.69(m,1H),4.06–4.00(m,1H),3.80(dd,J=11.7,7.5Hz,1H),3.45(dd,J=15.2,11.7Hz,1H),2.78–2.64(m,2H),2.41(s,3H),2.31(s,3H),2.31(s,3H),1.49(s,
9H).13C NMR(100MHz,CDCl3):δ169.33,143.29,140.11,137.60,136.75,136.58,134.38,
133.46,129.57,129.31,128.87,128.75,127.99,127.28,127.07,81.61,51.78,45.77,
42.22,41.61,28.16,21.57,21.19,18.96.HRMS(ESI-TOF):理论计算值:C30H35NaNSO4[M+Na+]528.2179,实测值:528.2176。
6.94(m,3H),6.90(t,J=7.5Hz,1H),6.47(d,J=7.7Hz,1H),5.72(dd,J=10.2,3.2Hz,1H),
4.05–3.99(m,1H),3.83(dd,J=11.6,7.5Hz,1H),3.45(dd,J=15.2,11.7Hz,1H),2.77–
2.63(m,2H),2.42(s,3H),2.38–2.35(m,1H),2.30(s,3H),1.49(s,9H),1.29(s,9H).13C NMR(100MHz,CDCl3):δ169.36,149.93,143.28,139.99,137.59,136.55,134.43,133.45,
129.31,128.74,128.58,128.07,127.33,127.05,125.75,81.60,51.71,45.77,42.12,
41.59,34.58,31.47,28.17,21.57,18.97.HRMS(ESI-TOF):理论计算值:C33H41NaNSO4[M+Na+]570.2649,实测值:570.2650。
0.1mmol),其他条件同实施例26,得化合物I-29(无色油状液体,产率41%)。H NMR(400MHz,CDCl3):δ7.60(d,J=8.3Hz,2H),7.25–7.24(m,2H),7.11–7.08(m,2H),6.99–6.96(m,3H),6.91(t,J=7.6Hz,1H),6.40(d,J=7.7Hz,1H),5.72–5.69(m,1H),4.03–3.99(m,
1H),3.86(dd,J=11.6,7.5Hz,1H),3.42(dd,J=15.1,11.6Hz,1H),2.75–2.63(m,2H),2.41(s,3H),2.31(s,3H),1.48(s,9H).13C NMR(100MHz,CDCl3):δ169.24,143.45,141.63,
137.48,135.86,134.44,133.70,132.96,130.35,129.39,129.09,127.88,127.29,127.23,
81.71,51.66,45.63,42.18,41.60,28.15,21.59,18.97.HRMS(ESI-TOF):理论计算值:
C29H32NaNClSO4[M+Na+]548.1633,实测值:548.1636。
0.1mmol),其他条件同实施例26,得化合物I-30(无色油状液体,产率40%)。H NMR(400MHz,CDCl3):δ7.62–7.60(m,2H),7.26–7.22(m,1H),7.10–7.08(m,2H),6.99(d,J=
7.3Hz,1H),6.95–6.90(m,2H),6.85–6.83(m,1H),6.72(dt,J=9.8,2.1Hz,1H),6.43(d,J=
7.7Hz,1H),5.73–5.70(m,1H),4.07–4.01(m,1H),3.87(dd,J=11.6,7.5Hz,1H),3.45(dd,J
19
=15.2,11.6Hz,1H),2.76–2.64(m,2H),2.42(s,3H),2.31(s,3H),1.48(s,9H). F NMR(377MHz,CDCl3)δ-112.49.13C NMR(100MHz,CDCl3):δ169.25,163.11(d,J=246.5Hz),
145.69(d,J=6.0Hz),143.45,137.47,135.62,134.43,133.69,130.40(d,J=8.0Hz),
129.39,129.12,127.93,127.30,127.24,124.75(d,J=3.0Hz),115.82(d,J=21.0Hz),
114.15(d,J=20.0Hz),81.70,51.67,45.54,42.49,41.56,28.15,21.59,18.97.HRMS(ESI-TOF):理论计算值:C29H32NaNFSO4[M+Na+]532.1928,实测值:532.1930。
反应容器冷却至室温后,用水(5mL)淬灭,用乙酸乙酯(3×5mL)萃取,Na2SO4干燥,过滤,真空下浓缩。用柱色谱纯化,洗脱剂为石油醚:乙酸乙酯=5:1(v/v),得到化合物I-31(无色油状液体,产率51%)。1H NMR(400MHz,CDCl3):δ7.35(d,J=8.3Hz,2H),6.97–6.93(m,3H),6.85(d,J=7.5Hz,1H),6.77(d,J=7.3Hz,1H),5.55(dd,J=10.2,5.2Hz,1H),4.29–4.13(m,
2H),3.90–3.80(m,1H),2.89–2.68(m,3H),2.53(dd,J=14.2,5.2Hz,1H),2.25(s,3H),2.20(s,3H),1.62(d,J=6.3Hz,3H),1.32(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3):δ170.12,
142.88,136.06,135.47,133.80,133.36,129.05,128.39,127.49,127.16,125.62,61.23,
52.74,51.19,40.65,35.20,26.11,21.49,18.42,14.37.HRMS(ESI-TOF):理论计算值:
C22H27NaNSO4[M+Na+]424.1553,实测值:424.1551。
15.7,7.5Hz,1H),2.80(dd,J=14.4,10.3Hz,1H),2.61(dd,J=15.7,10.8Hz,1H),2.51(dd,J=14.5,5.0Hz,1H),2.24(s,3H),2.23–2.20(m,1H),2.19(s,3H),1.90–1.78(m,1H),1.32(t,J=7.1Hz,3H),1.04(t,J=7.5Hz,3H).13C NMR(100MHz,CDCl3):δ170.11,142.81,
136.08,135.61,133.58,133.37,128.99,128.29,127.42,127.16,125.83,61.23,56.48,
52.57,40.30,33.31,32.32,21.48,18.40,14.37,10.63.HRMS(ESI-TOF):理论计算值:
C23H29NaNSO4[M+Na+]438.1710,实测值:438.1710。
79–3.73(m,1H),2.98–2.92(m,2H),2.76(dd,J=14.6,11.4Hz,1H),2.64(dd,J=16.0,
10.0Hz,1H),2.50(dd,J=14.6,4.6Hz,1H),2.23(s,3H),2.19(s,3H),2.13–2.05(m,1H),
13
2.04–1.96(m,1H),1.36(t,J=7.1Hz,3H). C NMR(100MHz,CDCl3):δ169.94,143.15,
135.19,134.93,133.42,133.29,129.01,128.21,127.48,127.08,125.84,61.44,58.44,
53.15,50.87,42.56,39.32,33.25,21.48,18.33,14.39.HRMS(ESI-TOF):理论计算值:
C23H29NaNSO5[M+Na+]454.1659,实测值:454.1659。
3.90–3.83(m,1H),3.73–3.61(m,2H),2.87–2.77(m,2H),2.75–2.71(m,1H),2.44(dd,J=
13.4,3.7Hz,1H),2.24(s,3H),2.20(s,3H),1.45(s,9H),1.37(d,J=7.2Hz,3H).13C NMR(100MHz,CDCl3):δ170.65,157.15,143.37,135.21,134.52,133.47,133.17,129.20,
128.35,127.69,127.19,125.95,79.18,61.66,56.19,53.31,46.26,40.63,29.68,28.62,
21.50,18.28,14.34.HRMS(ESI-TOF):理论计算值:C27H36NaN2SO6[M+Na+]539.2186,实测值:
539.2189。
7.4Hz,1H),5.54(dd,J=10.1,4.9Hz,1H),4.21(qd,J=7.2,3.3Hz,2H),3.91–3.86(m,2H),
3.75–3.70(m,1H),3.45(s,3H),2.98–2.84(m,3H),2.49(dd,J=14.6,4.9Hz,1H),2.24(s,
3H),2.20(s,3H),1.31(s,3H).13C NMR(100MHz,CDCl3):δ170.19,143.08,135.57,135.51,
133.29,133.24,129.06,128.28,127.49,127.20,125.86,77.65,61.11,59.30,54.09,
52.28,40.42,30.53,21.47,18.39,14.35.HRMS(ESI-TOF):理论计算值:C23H29NaNSO5[M+Na+]454.1659,实测值:454.1657。
5.54(dd,J=9.8,5.0Hz,1H),4.67–4.61(m,2H),4.18(qd,J=7.1,1.9Hz,2H),4.03–3.99(m,1H),3.98–3.92(m,1H),3.86(t,J=8.2Hz,1H),3.01(dd,J=15.9,7.1Hz,1H),2.89(dd,J=14.6,9.9Hz,2H),2.50(dd,J=14.6,5.0Hz,1H),2.24(s,3H),2.20(s,3H),1.28(t,J=
7.1Hz,3H).13C NMR(100MHz,CDCl3):δ170.20,143.09,138.39,135.61,135.55,133.33,
133.28,129.07,128.54,128.30,127.85,127.79,127.50,127.22,125.86,75.59,73.62,
61.11,54.24,52.30,40.54,30.71,21.49,18.42,14.34.HRMS(ESI-TOF):理论计算值:
C29H33NaNSO5[M+Na+]530.1972,实测值:530.1972。
5.51(dd,J=9.3,5.2Hz,1H),4.23–4.12(m,2H),4.09(dd,J=9.8,3.7Hz,1H),3.94(dd,J=
9.9,7.8Hz,1H),3.85–3.78(m,1H),2.98–2.82(m,3H),2.51(dd,J=14.7,5.2Hz,1H),2.25(s,3H),2.18(s,3H),1.28(t,J=7.1Hz,3H),0.95–0.93(m,9H),0.14(d,J=1.2Hz,6H).13C NMR(100MHz,CDCl3):δ170.24,143.03,135.83,135.75,133.61,133.36,129.08,128.27,
127.46,127.23,125.90,68.29,61.06,56.08,52.11,40.83,30.32,26.13,21.50,18.52,
18.47,14.33,-5.15,-5.18.HRMS(ESI-TOF):理论计算值:C28H41NaSiNSO5[M+Na+]554.2367,实测值:554.2365。
0.1mmol),其他条件同实施例31,得化合物I-38(无色油状液体,产率41%)。H NMR(400MHz,CDCl3):δ7.35–7.31(m,4H),7.05–7.03(m,2H),7.01–6.91(m,4H),6.87–6.85(m,
1H),6.77(d,J=7.4Hz,1H),5.63(dd,J=10.5,4.6Hz,1H),4.58(dd,J=9.5,3.8Hz,1H),
4.31(t,J=9.2Hz,1H),4.13–4.05(m,1H),3.07(dd,J=15.9,7.5Hz,1H),2.92(dd,J=
15.9,11.1Hz,1H),2.82(dd,J=14.4,10.6Hz,1H),2.49(dd,J=14.5,4.7Hz,1H),2.27(s,
3H),2.23(s,3H),1.53(s,9H).13C NMR(100MHz,CDCl3):δ169.36,158.45,143.17,135.82,
135.19,133.24,132.87,129.69,129.10,128.39,127.51,127.25,125.93,121.09,114.69,
81.69,72.31,53.20,52.76,41.50,30.52,28.21,21.47,18.43.HRMS(ESI-TOF):理论计算值:C30H35NaNSO5[M+Na+]544.2128,实测值:544.2124。
7.3Hz,1H),2.36(dd,J=13.0,3.4Hz,1H),2.28(s,3H),2.23(s,3H),1.61(s,9H).13C NMR(100MHz,CDCl3):δ171.04,143.21,135.10,134.71,133.79,132.95,129.10,128.16,
127.59,127.20,126.03,82.95,66.27,57.44,53.55,41.46,28.23,27.98,21.48,
+
18.23.HRMS(ESI-TOF):理论计算值:C24H31NaNSO5[M+Na]468.1815,实测值:468.1818。