具有胆碱酯酶抑制活性的异色满-4-酮类衍生物、其制备方法及医药用图_4

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: (ESI, pos. ion) m/z :433. I [M]+;HRMS (ESI) calculated for C24H21N2O/[M]+433. 1394, found 433. 1395.
[0106] 实施例17
[0107] (Z)-I-苄基-4-((7-甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)吡啶-I-鑰 溴化物(VIIn).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :9. 11 (d,J = 6·75Ηζ,2H),8.42 (d, J = 6. 69Hz,2H),7. 96 (d,J = 9. 45Hz,1H),7. 56 (d,J = I. 77Hz,2H),7. 53 (d,J = I. 26Hz, 3H),7.11(d,J = 6.51Hz,,2H),6.97(s,lH),5.82(s,2H),5.57(s,2H),3.89(s,3H);13C NMR(75MHz,DMS0-d 6) δ :176. 77,164. 47,156. 44,150. 06,144. 04,141. 90,134. 54,129. 26, 129. 17,128. 64,126. 75,121. 11,115. 87,108. 79,104. 84,67· 38,62· 27,56· 02 ;MS-ESI : (ESI,pos. ion)m/z :358. I [Μ]+;HRMS (ESI) calculated for C23H20NO/[Μ]+358· 1438, found 358. 1436.
[0108] 实施例18
[0109] (Z)-I-(2-氟苄基)-4-((7-甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)吡 啶-1-鑰溴化物(VIIo).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :9.00(d,J = 6.75Hz,2H), 8· 43 (d,J = 6. 87Hz,2H),7· 98 (d,J = 8. 43Hz,1H),7· 57 (m,2H),7· 34 (m,2H),7· 14 (m,2H), 6.99(s,lH),5.89(s,2H),5.58(s,2H),3.91(s,3H) ;13C NMR(75MHz,DMS0-d6) δ :176.93, 164. 48,158. 78,156. 61,150. 34,144. 23,142. 96,141. 89,132. 02,131. 90,129. 42,129. 28, 126. 72,125. 28,125. 23,121. 11,116. 10,115. 88,115. 83,108. 79,104. 77,67· 40,57· 02, 56. 02, 55. 87 ;MS-ESI : (ESI,pos. ion)m/z :376. I [Μ]+;HRMS (ESI) calculated for C23H19FN 03+[M]+376. 1343, found376. 1337.
[0110] 实施例19
[0111] (Z)-l_(3-氟苄基)-4-((7-甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基) 吡啶-1-鑰溴化物(VIIp).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :9. 11 (d,J = 4·02Ηζ, 2H),8· 42 (d,J = 4. 08Hz,2H),7· 98 (m,1H),7· 48 (d,J = 8. 10Hz,2H),7· 39 (d,J = 7. 26Hz, 1Η),7· 27(t,J = 8· 46Hz,1Η),6· 98(s,2H),6· 97(s,1Η),5· 83(s,2H),5· 57(s,2H),3· 89(d, J = 2·31Ηz,3Η) ;13C 匪 R(75MHz,DMS0-d6) δ :176. 76,164·47,156·51,150·19,144· 12, 141. 90,136. 87,131. 35,131. 24,129. 27,126. 78,124. 84,121. 11,116. 28,115. 87,115. 61, 108. 78,104. 81,67. 39,61. 47,56. 01 ;MS-ESI : (ESI, pos. ion)m/z :376. I [M]+;HRMS(ESI) calculated for C23H19FNO3"[M]+376. 1343, found 376. 1336.
[0112] 实施例20
[0113] (Z)-1-(4-氟苄基)-4-((7-甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基) 吡啶-1-鑰溴化物(VIIq).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :9· 13 (d,J = 6·81Ηz, 2H),8· 43 (d,J = 6. 81Hz,2H),7· 98 (d,J = 3. 39Hz,1H),7· 68 (m,2H),7· 31 (t,J = 8. 85Hz, 2H),7.12(m,2H),6.98(s,lH),5.84(s,2H),5.59(s,2H),3.91(s,3H) ;13C 匪R(75MHz, DMS0-d6) δ :176. 75, 164. 44,164. 10,160. 84,156. 44,150. 05,143. 94,141. 89,131. 36, 131. 25,130. 79,129. 25,126. 74,121. 08,116. 21,115. 92,115. 86,108. 76,104. 80,67· 37, 61.34,56.01 ;MS-ESI :(ESI, pos. ion)m/z :376. I [M]+;HRMS (ESI) calculated for C23H19FN 03+[M]+376. 1343, found376. 1340.
[0114] 实施例21
[0115] (Z)-l_(2-甲氧基苄基)-4-((7-甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲 基)吡啶-1-鑰溴化物(VIIr).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :9. 12(d,J = 6. 66Hz, 2H),8.41(d,J = 6.69Hz,2H),7.96(t,J = 4.77Hz,lH),7.36(t,J = 7.8Hz,lH),7.2(s, 1H),7. 10(m,3H),6. 97(m,2H),5. 77(s,2H),5. 57(s,2H),3. 89(s,3H),3. 76(s,3H),13C NMR(75MHz,DMS0-d6) δ :176. 76,164. 45,159. 62,156. 43,150. 03,144. 01,141. 89,135. 84, 130. 38,129. 26,126. 70,121. 10,120. 67,115. 86,114. 66,114. 53,108. 77,104. 84,67· 37, 62. 18,56. 01,55. 25 ;MS-ESI : (ESI,pos. ion)m/z :388. 2 [M]+;HRMS (ESI) calculated for C 24H22N04+[M]+388. 1543, found388. 1543.
[0116] 实施例22
[0117] (Z)-I-(3-甲氧基苄基)-4-((7-甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲 基)吡啶-1-鑰溴化物(VIIs).黄色固体; 1H NMR(300MHz,DMSO-(I6) δ :9· 07 (d,J = 6. 8IHz, 2H),8.41(d,J = 6.84Hz,2H),7.98(d,J = 8.49Hz,lH),7.36(t,J = 7·89Ηζ,1Η),7· 10(m, 4H),7· 00(m,2H),5· 74(s,2H),5· 57(s,2H),3· 90(s,3H),3· 77(s,3H) ;13C 匪R(75MHz, DMS0-d6) δ :176. 73, 164. 42,159. 60,156. 39,149. 98,143. 99,141. 87,135. 86,130. 35, 129. 23,126. 67,121. 06,120. 70,115. 85,114. 67,114. 55,108. 75,104. 84,67. 36,62. 09, 56. 01,55. 26 ;MS-ESI : (ESI,pos. ion)m/z :388. 2 [M]+;HRMS (ESI) calculated for C24H22NO4 + [M]+388. 1543, found388. 1544.
[0118] 实施例23
[0119] (Z)-l_(4-甲氧基苄基)-4-((7-甲氧基-4-氧代异苯并二氢吡喃-3-亚基) 甲基)吡啶-1-鑰溴化物(VIIt).黄色固体; 1H NMR(300MHz,DMSO-(I6) δ :9. 19(d,J = 6.63Hz,2H),8.39(d,J = 6.63Hz,2H),7.96(d,J = 9.39Hz,lH),7.59(d,J = 8·61Ηz, 2H),7· 10 (m,2H),6· 99 (m,3H),5· 80 (s,2H),5· 57 (s,2H),3· 90 (s,3H),3· 76 (s,3H) ;13C NMR(75MHz,DMS0-d6) δ :176. 77,164. 43,159. 86,156. 29,149. 80,143. 82,141. 89,130. 57, 129. 23,126. 65,126. 51,121. 07,115. 83, 114. 47,108. 74,104. 88,67· 33,61· 75,55· 99, 55.21 ;MS-ESI : (ESI,pos. ion)m/z :388. 2 [Μ]+;HRMS (ESI) calculated for C24H22NO/ [M]+388. 1543, found 388.1545.
[0120] 实施例24
[0121] (Z)-I-(2-氯苄基)-4-((7-甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)吡 啶-1-鑰溴化物(VIIu).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :8.98(d,J = 6.81Hz,2H), 8. 44(d,J = 6· 81Hz,2H),7· 97(m,1H),7· 60(d,J = 7. 02Hz,1H),7· 5(m,3H),7· 12(m,2H), 7.00(s,lH),5.94(s,2H),5.58(s,2H),3.90(s,3H) ;13C NMR(75MHz,DMS0-d6) δ :176.72, 164. 47,156. 67,150. 40,144. 43,141. 91,133. 12,131. 70,131. 31,131. 04,129. 27,128. 13, 126. 61,121. 09,115. 90,108. 78,104. 74,67· 41,60· 26,56· 03 ;MS-ESI : (ESI,pos. ion)m/ Z :392. I [M]+;HRMS (ESI) calculated for C23H19ClNO/[Μ]+392· 1048, found 392. 1050.
[0122] 实施例25
[0123] (Z)-I-(3-氯苄基)-4-((7-甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)吡 啶-1-鑰溴化物(VIIv).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :9. ll(d,J = 6· 75Hz,2H), 8.42(d,J = 6.75Hz,2H),7.97(m,lH),7.72(s,lH),7.5(m,3H),7. ll(d,J = 6·48Ηζ,2Η), 6.98(s,lH),5.82(s,2H),
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