一种螺环羟吲哚咪唑啉并氧氮杂卓化合物及其合成方法_3

文档序号:9410214阅读:来源:国知局
SI-MS:m/z[M+Na]+calcdforC34H22ClN303Na+: 578.1242; found: 578. 1244.以上数据证明目的产物合成成功。
[0036] 实施例八:
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(ID(3. 5mg,0? 01mmol)作为催化剂,la(43.lmg, 0? 22mmol),2h(23. 6mg, 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3h(收率分别为46. 9mg,90 %,43. 2mg, 83%yield),白色固体,非对映选择性>99/1。
[0037]对产物 3h进行分析,结果如下:4NMR(400MHz,CDC13)S7.44 (s, 1H), 7.38 (d, /= 8.0Hz, 1H), 7.24 - 7.22 (m, 2H), 7.20 - 7.11 (m, 3H), 7.10-6.93 (m, 8H), 6.83 - 6.79 (m, 1H), 6.75 (d,/ = 1.6Hz, 1H), 6.63 (td,J =7.2, 1.6Hz, 1H), 6.58 (td, / = 7.6, 1.6Hz, 1H), 5.83 (dd, / = 8.0, 1.6Hz, 1H), 5. 12 (s, 1H).13CNMR(101MHz,CDC13) 8 177.15, 159.05, 155.83, 154.05, 145.54, 140.04, 137.28, 135.22, 130.11, 129.83, 129.22, 127.85, 127.19, 126.79, 126.56, 126.49, 125.84, 125.78, 125.52, 124.84, 123.86, 122.96, 122.79, 122.54, 121.67, 121.58, 121.21, 120.28, 118.97, 113.97, 113.39, 73.89, 73.22, 72.38.IR(neat,cm1): 3196, 3064, 3037, 2815, 1722, 1606, 1576, 1490, 1455, 1315.ESI-MS:m/z[M+Na]+calcdforC34H22BrN303Na+: 622. 0737;found: 622. 0750.以上数据证明目的产物合成成功。
[0038] 实施例九:
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),2i(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3i(收率分别为46.8mg,90%,45. 4mg,87% yield),白色固体,非对映选择性>99/1。
[0039]对产物3i进行分析,结果如下:4NMR(400MHz,CDC13)S9.05 (s, 1H), 7.43 (d, /=8.4Hz, 2H), 7.24 - 7.16 (m, 5H), 7.11 - 6.99 (m, 6H), 6.94 (dd, / = 5. 2, 2. 4Hz, 1H), 6. 83 - 6. 77 (m, 2H), 6. 62 - 6. 54 (m, 3H), 5. 84 (dd,J =8.0,1.6Hz, 1H), 5.12 (s, 1H).13CNMR(101MHz,CDC13)S177.69,159.03, 155.82, 154.04, 145.54, 139.92, 137.28, 135.25, 135.06, 130.11, 129.81, 129.22, 127.81, 126.80, 125.99, 125.84, 125.77, 125.53, 124.84, 123.87, 123.56, 122.80, 122.56, 121.66, 121.55, 121.20, 120.27, 118.94, 113.94, 110.82, 73.92, 73.27, 72.39.IR(neat,cm1): 3196, 3064, 3037, 2815, 1722, 1606, 1576, 1490, 1455, 1389, 1367, 1315, 1292.ESI-MS:m/z[M+Na]+calcd forC34H22ClN303Na+: 578.1242;found: 578.1232.以上数据证明目的产物合成成功。
[0040] 实施例十:
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(ID(3.5mg,0.01mmol)作为催化剂,la(39. 2mg, 0.20mmol),2j(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3j(收率分别为44. 9mg,86%,41. 7mg,80% yield),白色固体,非对映选择性>99/1。
[0041]对产物 3j进行分析,结果如下:4NMR(400MHz,DMSO)S11. 36 (s, 1H), 7.40 (s, 1H), 7.33 - 7.28 (m, 3H), 7.26 (d,J=3.6,Hz, 1H), 7.22 (dd,J= 7.6, 1.2Hz, 1H), 7.18 - 7.13 (m, 3H), 7.11 (d,/ =2.0Hz, 1H), 7.10 (t,J = 2.8Hz, 1H), 7.07 - 7.04 (m, 3H), 6.97 - 6.91 (m, 2H), 6.75 (td,J=7.7, 9. 2Hz, 1H), 6.71 (d, / = 8. 4, 1H), 6.59 (td, / = 7. 6, 1. 2Hz, 1H), 5.76 (dd, /=8.0, 1.2Hz, 1H), 4.98 (s, 1H).13CNMR(101MHz,DMSO) 8 174.87, 158.52, 155.31, 153.49, 144.66, 139.48, 136.72, 134.87, 130.28, 129.79, 129.44, 128.99, 128.85, 127.69, 125.94, 125.87, 125.83, 125.67, 125.57, 124.81, 124.33, 123.80, 122.40, 122.22, 122.10, 121.20, 120.80, 120.27, 118.40, 113.49, 111.40, 73.21, 72.23, 71.45.IR(neat,cm1): 3164, 3120, 3066, 2850, 2821, 1718, 1619, 1490,1455, 1393, 1370, 1320.ESI-MS:m/z[M+Na]+calcdfor C34H22ClN303Na+: 578. 1242;found: 578. 1240.以上数据证明目的产物合成成功。
[0042]实施例 ^^一:
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),2k(18.9mg, 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=1:1)即可得到目标产物3k(收率分别为48. 9mg,94%,47. 4mg,91% yield),白色固体,非对映选择性>99/1。
[0043]对产物 3k进行分析,结果如下:4NMR(400MHz,DMSO)S11.03 (s, 1H), 7.40 (s, 1H), 7.32 - 7.27 (m, 3H), 7.20 (dd,J = 8.0, 1.6Hz, 1H), 7.16 - 7.09 (m, 5H), 7.06 - 7.03 (m, 2H), 6.99 (d,J= 7.2, 1H), 6.96 (s, 1H), 6.91 (td, /= 6.8, 2.0Hz, 1H), 6.72 (td, / = 5. 2, 1.6 Hz, 1H), 6.61(d, /= 1.6Hz, 2H), 6.56 (td, /=8.0, 1. 2Hz, 1H), 5.85 (dd, / = 8.0, 0.8Hz, 1H), 4.96 (s, 1H), 3.51 (s, 3H).13CNMR(101MHz,DMSO) 8 174.98, 158.54, 155.30, 154.74, 153.54, 144.59, 136.93, 135.06, 133.84, 130.16, 129.51, 129.18, 127.96, 127.81, 125.87, 125.74, 125.61, 125.48, 124.63, 123.69, 122.78, 122.05, 121.96, 121.15, 120.77, 120.19, 118.04, 114.10, 113.68, 111.40, 110.24, 73.37, 72.05, 71.34, 55.11.IR(neat,cm1): 3165.22, 3132.47, 3063.19, 3042.15, 2955.52, 2848.83, 1709.70, 1599.65, 1485.85, 1455.26, 1387.44, 1366.57, 1316.20, 1291.06.ESI-MS:m/z[M+Na]+calcdforC34H22ClN303Na+: 578. 1242;found: 578. 1236.以上数据证明目的产物合成成功。
[0044] 实施例十二:
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),21 (18.7mg, 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=1:1)即可得到目标产物31 (收率分别为48. 5mg,93%,45. 8mg,88% yield),白色固体,非对映选择性>99/1。
[0045]对产物 31 进行分析,结果如下:4NMR(400MHz,DMSO)S11. 14 (s, 1H), 7.38 (s, 1H), 7.31 - 7.26 (m, 3H), 7.20 (dd, / = 7.6, 1.2 Hz, 1H), 7.15 - 7.07 (m, 5H), 7.03 (dd,J= 10.4, 7. 2Hz, 2H), 7.03 - 6.97 (m, 2H), 6.88 (td, /= 8.8, 1.6Hz, 1H), 6.72 (td, / = 9. 2, 1. 2 Hz, 1H), 6.65 (s, 1H), 6.56 (t, J=7.2, 1H), 5.85 (d, / = 7. 2Hz, 1H), 4.94 (s, 1H), 2.06 (s, 3H), 1.98 (s, 3H).13CNMR(101MHz,DMSO) 8 175.78, 158.49, 155.29, 153.47, 144.52, 137.11, 136.75, 135.27, 131.11, 130.45, 130.07, 129.43, 129.17, 127.64, 126.50, 126.13, 125.70, 125.55, 125.40, 124.55, 123.27, 122.93, 122.50, 121.99, 121.83, 120.97, 120.76, 120.10, 118.64, 117.92, 113.91, 73.61, 72.44, 71.50, 20.62, 16.00.IR(neat,cm1): 3184, 3080, 3039, 2811, 1714, 1629, 1602, 1576, 1493, 1455, 1385, 1368, 1316, 1290.ESI-MS:m/z[M+Na]+calcdfor C35H25N304Na+: 572. 1945;found: 572. 1943.以上数据证明目的产物合成成功。 [0046] 实施例十三:
反应瓶
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