一种螺环羟吲哚咪唑啉并氧氮杂卓化合物及其合成方法_2

文档序号:9410214阅读:来源:国知局
):calcd.forC35H25N303Na+[M+Na]+ 558.1788;found: 558.1768.以上数据证明 目的产物合成成功。
[0025] 实施例三:
反应瓶中依次加入对甲苯磺酸一水合物(1. 9mg,0. 01mmol),la(43.lmg, 0. 22mmol),2c(24.9mg, 0.1mmol),加入2mL乙醚,在室温条件下搅拌反应24小时,反应体系 通过简单的柱层析(洗脱剂为二氯甲烷:石油醚=1:1)即可得到目标产物3c(收率为47. 9 mg,92%),白色固体,非对映选择性>99/1。
[0026] 反应瓶中依次加入三氟甲磺酸铁(II) (3.5mg,0.01mmol),la(43.lmg,0.22 mmol),2c(24. 9mg, 0.1mmol),加入2mL四氢咲喃,在室温条件下搅拌反应24小时,反 应体系通过简单的柱层析(洗脱剂为二氯甲烷:石油醚=1:1)即可得到目标产物3c(收率为 46. 3mg,89%),白色固体,非对映选择性>99/1。
[0027] 对产物 3c进行分析,结果如下:虫NMR(400MHz,CDC13)S7. 54 - 7. 48 (m, 4H), 7.42 - 7.33 (m, 3H), 7.25 - 7.20 (m, 4H), 7.15(dd, / =7.6, 1.6Hz, 1H), 7.08 - 6.93 (m, 7H), 6.83(td, / = 7.6, 0.8Hz, 1H), 6. 78(dd,J=8.0, 1.2Hz, 1H), 6.66(d, / =8.0, 1H), 6.60(td, / =7.6, 1. 2Hz, 1H), 6.55(td,J=7.6,1.6Hz, 1H), 6.48(td,/=8.0, 1.6Hz, 1H), 5.64(dd,/=8.0, 1.2Hz, 1H), 5.36 (d, J=15.2 Hz, 1H), 5.17 (s,1H), 4.63 (d,J=14.8 Hz, 1H). 13CNMR (101 MHz, CDC13) 8 174.82, 159.09, 155. 79, 153.98, 145.42, 141. 32, 137. 54, 135.55, 135.34, 129.94, 129.35, 129.31, 129.04, 128.89, 128.25, 127.93, 126.92, 126.87, 125.70, 125.68, 125.61, 125.38, 124.60, 123.36, 123.31, 123.15, 122.22, 121.63, 121.26, 121.14, 120.22, 118.53, 114.58, 108.59, 73.63, 73.27, 72.31, 44.89.IR(neat,cm1): 3063, 3035, 2922, 2848, 2803, 2758, 1719, 1599, 1576, 1490, 730, 1030.HRMS(ESI) :calcd.forC41H29N303Na+[M +Na]+ 634.2101;found: 634. 2129.以上数据证明目的产物合成成功。
[0028]实施例四:
反应瓶中依次加入对甲苯磺酸一水合物(1.9mg,0. 01mmol)或者三氟甲磺酸铁(II) (3. 5mg,0? 01mmol)作为催化剂,la(43.lmg, 0? 22mmol),2d(26. 3mg, 0? 1mmol), 加入2mL对二甲苯,在室温条件下搅拌反应24小时,反应体系通过简单的柱层析(洗脱剂 为二氯甲烷:石油醚=1:1)即可得到目标产物3d(收率分别为47. 8mg,92 %,45. 3mg, 87%yield),白色固体,非对映选择性>99/1。
[0029]对产物 3d进行分析,结果如下:4NMR(400MHz,CDC13)S7. 79 (d,/ = 7.6Hz, 2H), 7.53 (dd,J=13.6, 7.2Hz, 2H), 7.44 (d, / = 8.0Hz, 1H), 7.37 (t, /=7.6Hz, 2H), 7.31 (s, 1H), 7.18 - 7.05 (m, 6H), 7.04 - 6.88 (m, 6H), 6.88 - 6.69 (m, 4H), 6.59 (t, /=7. 2Hz, 1H), 6.01 (d, / = 8.0Hz, 1H), 5.03 (s, 1H).13CNMR(101MHz,CDC13)S175.42,168.86,158.93,155.66,153.93, 145.78, 138.57, 137.26, 135.57, 133.55, 130.12, 130.05, 129.77, 129.75, 129.06, 128.43, 128.00, 127.40, 126.95, 126.91, 125.73, 125.71, 125.52, 125.49, 125.45, 124.83, 124.09, 123.26, 122.90, 122.75, 121.58, 121.53, 121.22, 120.29, 119.31, 116.09, 114.61, 114.28, 74.47, 74.42, 72.55.IR(neat, cm1): 3183,3153,3079,3062,1716,1621,1498,1454,1392,1368.HRMS(ESI):calcd.forC41H27N304Na+[M+Na]+ 648. 1894;found: 648. 1924?以上数据证明目的产物 合成成功。
[0030] 实施例五:
反应瓶中依次加入对甲苯磺酸一水合物(1.9mg,0. 01mmol)或者三氟甲磺酸铁(II) (3.5mg,0.01mmol)作为催化剂,la(43.lmg, 0.22mmol),2e(25.9mg, 0.1mmol),加 入2mL1,4-二氧六环,在室温条件下搅拌反应24小时,反应体系通过简单的柱层析(洗脱 剂为二氯甲烷:石油醚=1:1)即可得到目标产物3e(收率分别为47. 5mg,91%,47. 1mg, 90%),白色固体,非对映选择性>99/1。
[0031]对产物 3e进行分析,结果如下:虫NMR(400MHz,CDC13)S7. 57 - 7. 53 (m, 2H), 7.44 (s, 1H), 7.25 - 7.10 (m, 6H), 7.09 - 6.98 (m, 5H), 6.97 - 6.91 (m,3H), 6.80 - 6.76(m,1H), 6.67 (td,/ = 7.6, 1.6Hz, 1H), 6.56 (td, J= 7.6, 1.4Hz, 1H), 5.70 (dd, / = 8.4, 1.6Hz, 1H), 5.13 (s, 1H), 1.69 (s, 9H). 13CNMR(101MHz, CDC13) 8 173.98, 159.03, 155.88, 153.93, 148.94, 145.42, 138.21, 137.26, 134.94, 130.06, 129.69, 129.12, 127.70, 126.88, 126.16, 125.93, 125.75, 125.43, 125.36, 124.99, 124.71, 123.47, 122.81, 122.39, 121.63, 121.43, 121.20, 120.28, 118.75, 114.45, 114.31, 85.01, 74.41, 74.03, 72.41, 28.27.IR(neat,cm1): 3063, 2961, 2923, 2851, 1772, 1731, 1689, 1600, 1490, 1465, 1454.ESI-MS:m/z[M+Na]+calcdforC39H31N305Na+: 644.2156;found: 644. 2157.以上数据证明目的产物合成成功。
[0032]实施例六:
反应瓶中依次加入对甲苯磺酸一水合物(1.9mg,0. 01mmol)或者三氟甲磺酸铁(II) (3.5mg,0.01mmol)作为催化剂,la(49mg, 0.25mmol),2f(17.3mg, 0.1mmol),加入 2mL四氢呋喃,在室温条件下搅拌反应24小时,反应体系通过简单的柱层析(洗脱剂为二 氯甲烷:石油醚=2:1)即可得到目标产物3f(收率分别为45. 8mg,88%,42. 2mg,81%), 白色固体,非对映选择性>99/1。
[0033]对产物3f进行分析,结果如下:4NMR(400MHz,DMS0)S11. 09 (s, 1H), 7.37 (s, 1H), 7.33 - 7.31 (m, 2H), 7.30 - 7.26 (m, 1H), 7.19 (dd,J=8.0, 1.2Hz, 1H), 7.17 - 7.06 (m, 6H), 7.05 - 7.02 (m, 2H), 6.96 (d, / = 7. 2Hz, 1H), 6.90 (td, /= 6.0, 2.0Hz, 1H), 6.83 (dd, / = 8.0, 0.8Hz 1H), 6.71 (td, /= 7.6, 1.6Hz, 1H), 6.58 - 6. 54(m, 2H), 5.81 (dd, / = 7.6, 1.2Hz 1H), 4.93 (s, 1H), 2.02 (s, 3H).13CNMR(101MHz,DMSO) 8 175.27, 158.51, 155.30, 153.49, 144.56, 138.18, 137.05, 135.21, 130.63, 130.11, 129.77, 129.45, 129.13, 127.68, 126.78, 126.10, 125.70, 125.59, 125.44, 125.18, 124.60, 123.64, 122.93, 122.05, 121.91, 121.06, 120.77, 120.11, 117.99, 113.72, 109.51, 73.27, 72.26, 71.46, 20. 72.IR(neat,cm1): 3165, 3065, 3034, 2860, 2819, 1715, 1600, 1455, 1320, 1300.ESI-MS:m/z[M+Na]+calcdfor C35H25N303Na+: 558. 1788;found: 558. 1786.以上数据证明目的产物合成成功。
[0034]实施例七:
反应瓶中依次加入对甲苯磺酸一水合物(1.9mg,0. 01mmol)或者三氟甲磺酸铁(II) (3. 5mg,0? 01mmol)作为催化剂,la(43.lmg, 0? 22mmol),2f(19. 3mg, 0? 1mmol), 加入2mL四氢呋喃,在室温条件下搅拌反应24小时,反应体系通过简单的柱层析(洗脱剂 为二氯甲烷:石油醚=2:1)即可得到目标产物3f(收率分别为47. 5mg,91%,44. 3mg, 85%),白色固体,非对映选择性>99/1。
[0035]对产物3g行分析,结果如下NMR(400MHz,DMSO)S11.65 (s, 1H), 7.40 (s, 1H), 7.32(d, /=3.6Hz, 2H), 7.28 - 7.25(m,1H), 7.21(dd,J=7.6, 1.2Hz, 1H), 7.13 - 7.03 (m, 8H), 6.97 - 6.90 (m, 2H), 6.82 - 6.74 (m, 2H), 6.58 (t, /= 7.6Hz, 1H), 5.75 (d, / = 8.4Hz, 1H), 4.97 (s, 1H).13CNMR(101 MHz,DMSO) 8 175. 31, 158. 50, 155. 28, 153.46, 144.64, 138. 13, 136. 79, 134.89, 130.20, 129.77, 129.47, 128.95, 128.73, 127.50, 126.12, 125.86, 125.65, 125.56, 124.77, 123.52, 123.29, 123.11, 122.38, 122.20, 122.07, 121.19, 120.76, 120.16, 118.34, 114.22, 113.53, 79.18, 73.78, 72.56, 71.53. 4.98 (s, 1H).IR(neat,cm1): 3065, 3039, 2955, 2817, 2107, 1726, 1619, 1601, 1491, 1453, 1387, 1316.E
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