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_3

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H); 13C NMR(75MHz,DMS0-d6)S : 176·85,159·61,157·53,155·88, 149. 97,144. 01,142. 32,135. 89,132. 48 ;130. 37,126. 71,124. 43,121. 08,120. 66,114. 65, 114. 52,113. 24,104. 95,63. 72,62. 13,60. 31,56. 31,55. 25 ;MS-ESI : (ESI,pos. ion)m/z : 418. 2 [M]+;HRMS (ESI) calculated for C 25H24N05+[M]+418. 1649, found 418. 1644.
[0090] 实施例9
[0091] (Z)-4-((7,8-二甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)-1-(3-甲氧 基苄基)吡啶-1-鑰溴化物(VIIf).黄色固体; 1H NMR(300MHz,DMSO-(I6) δ :9· 15 (d,J = 6.6Hz,2H),8.42(d,J = 6.6Hz,2H),7.83(d,J = 8.73Hz,lH),7.33(m,2H),7.21(s,lH), 7. 10 (d,J = 7. 56Hz,1H),6. 99 (m,2H),5. 78 (s,2H),5. 59 (s,2H),3. 95 (s,3H),3. 81 (s,3H), 3.71(s,3H) ;13C NMR(75MHz,DMS0-d6) δ :177·35,160·11,158·04,156·38,150·48,144·51, 142. 87,136. 38,132. 98,130. 88,127. 22,124. 93,121. 58,121. 16,115. 15,115. 02,113. 75, 105. 45,64· 23,62· 64,60· 81,56· 81,55· 75 ;MS-ESI : (ESI,pos. ion)m/z :418. 2[M]+; HRMS (ESI) calculated for C25H24NOg+[M]+418. 1649, found 418. 1645.
[0092] 实施例10
[0093] (Z)-4_((7,8-二甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)-1-(4-甲氧 基苄基)吡啶-1-鑰溴化物(VIIg).黄色固体; 1H NMR(300MHz,DMSO-(I6) δ :9.20 (d,J = 6· 69Hz,2H),8· 39(d,J = 6· 72,2H),7· 82(d,J = 8. 73Hz,1H),7· 58(d,J = 8· 61Hz,2H), 7· 29(d,J = 8· 82Hz,1Η),6· 97(t,J = 8· 64Ηζ,3Η),5· 78(s,2H),5· 57(s,2H),3· 95(s,3H), 3.80(s,3H),3.74(s,3H) ;13C NMR(75MHz,DMS0-d6) δ :176. 85,159. 86,157. 52,155. 75, 149. 77,143. 84,142. 32,132. 46,130. 54,126. 67,126. 54,124. 41,121. 07,114. 47,113. 23, 105. 00,63· 69,61· 75,60· 30,56· 29,55· 21 ;MS-ESI : (ESI,pos. ion)m/z :418. 2[M]+; HRMS (ESI) calculated for C25H24NOg+[M]+418. 1649, found 418. 1643.
[0094] 实施例11
[0095] (Z)-4-((7,8-二甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)-1-(2-氯苄 基)吡啶-1-鑰溴化物(VIIh).黄色固体; 1H NMR(300MHz,DMSO-(I6) δ :9· 02 (d,J = 6. 48Hz, 2H),8· 45(d,J = 6· 45Hz,2H),7· 82(d,J = 8. 67Hz,1H),7· 59(d,J = 7. 41Hz,1H),7· 5(m, 3H),7.3(d,J = 7· 14Ηζ,1Η),6.98 (s,lH),5.98 (s,2H),5.60 (s,2Η),3.95 (s,3H),3.81 (s, 3H) ;13C NMR(75MHz,DMS0-d6) δ :176. 77,157. 54,156. 08,150. 34,144. 42,142. 34,133. 31, 132. 45,131. 72,131. 30,130. 03,128. 12,126. 61,124. 42,121. 06,113. 28,104. 86,63· 78, 60. 32,60. 20,56. 34 ;MS-ESI : (ESI,pos. ion)m/z :422. I [M]+;HRMS (ESI) calculated for C 24H21ClN04+[M]+422. 1154, found 422. 1146.
[0096] 实施例12
[0097] (Z)-4_((7,8-二甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)-1-(3-氯 苄基)吡啶-1-鑰溴化物(VIIi).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :9. 14(d,J = 6.39Hz,2H),8.43(d,J = 6.33Hz,2H),7.83(d,J = 8.73Hz,lH),7.73(s,lH),7.49(m, 3H),7. 32 (d,J = 8. 82Hz,1H),6. 97 (s,1H),5. 83 (s,2H),5. 60 (s,2H),3. 96 (s,3H),3. 81 (s, 3H) ;13C NMR(75MHz,DMS0-d6) δ :176. 84,157. 55,155. 97,150. 15,144. 11,142. 36,136. 70, 133. 61,132. 47,131. 06,129. 21,128. 72,127. 46,126. 81,124. 42,121. 10,113. 28,104. 94, 63. 76,61. 37,60. 32,56. 32 ;MS-ESI : (ESI,pos. ion)m/z :422. I [M]+;HRMS (ESI) calculated for C24H21ClNO4"[M]+422. 1154, found 422. 1150.
[0098] 实施例13
[0099] (Z)-4_((7,8-二甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)-1-(4-氯苄 基)吡啶-1-鑰溴化物(VIIj).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :9. 12(d,J = 5. 97Hz, 2H),8· 43(d,J = 6· 06Hz,2H),7· 83(d,J = 8. 55Hz,1H),7· 5(m,4H),,7· 31(d,J = 8. 7Hz, 1Η),6· 97(s,1Η),5· 83(s,2H),5· 59(s,2H),3· 96(s,3H),3· 81 (s,3H) ;13C 匪R(75MHz, DMS0-d6) δ :176. 93, 157. 54,155. 94,150. 07,144. 04,133. 43,132. 46,130. 70,129. 12, 126. 75, 124. 43, 121. 06, 113. 24, 104. 88,63· 72,61· 30,60· 30,56· 30 ;MS-ESI : (ESI, pos. ion) m/z :422. I [Μ]+;HRMS (ESI) calculated for C24H21ClNO/[Μ]+422· 1154, found 422. 1147.
[0100] 实施例14
[0101] (Z)-4-((7,8-二甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)-1-(2-硝基苄 基)吡啶-1-鑰溴化物(VIIk).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :.98 (d,J = 6·72Ηζ, 2H),8· 50 (d,J = 6. 75Hz,2H),8· 26 (d,J = 7. 98Hz,1H),7· 8 (m,3H),7· 32 (d,J = 8. 82Hz, 1H),7· 19 (d,J = 7. 68Hz,1H),7· 02 (s,1H),6· 18 (s,2H),5· 62 (s,2H),3· 96 (s,3H), 3.82(s,3H) ;13C NMR(75MHz,DMS0-d6) δ :176·82,157·57,156·17,150·48,147·46,144·70, 142. 34,134. 93,132. 49,130. 39,130. 22,129. 46,126. 69,125. 58,124. 47,121. 09,113. 29, 104. 87,63. 79,60. 33,56. 71,56. 33 ;MS-ESI : (ESI, pos. ion)m/z :433. I [M]+;HRMS (ESI) calculated for C24H21N2Og+[M]+433. 1394, found 433. 1390.
[0102] 实施例15
[0103] (Z)-4-((7,8-二甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)-1-(3-硝基苄 基)吡啶-1-鑰溴化物(VIII).黄色固体; 1H NMR(300MHz,DMSO-(I6) δ :9· 18 (d,J = 6. 63Hz, 2H),8· 54(s,1H),8· 44(d,J = 6· 60Hz,2H),8· 27(d,J = 8. 16Hz,1H),8· 05(d,J = 7. 65Hz, 1Η),7· 78 (m,2Η),7· 31 (d,J = 8· 76Hz,1Η),6· 97 (s,1Η),5· 97 (s,2Η),5· 59 (s,2Η),3· 95 (s, 3H),3.80(s,3H) ;13C NMR(75MHz,DMS0-d6) δ :177·32,158·05,156·54,150·74,148· 49, 144. 68,142. 83,136. 71,136. 05,132. 97,131. 26,127. 33,124. 94,124. 60,124. 54,121. 57, 113. 76,105. 35,64· 25,61· 52,60· 82,56· 82 ;MS-ESI : (ESI,pos. ion)m/z :433. I[M]+; HRMS (ESI) calculated for C24H21N2O/[Μ]+433· 1394, found 433. 1389.
[0104] 实施例16
[0105] (Z)-4-((7,8-二甲氧基-4-氧代异苯并二氢吡喃-3-亚基)甲基)-1-(4-硝基苄 基)吡啶-1-鑰溴化物(VIIm).黄色固体; 1H NMR(300MHz,DMS0-d6) δ :9. 15(d,J = 5. 79Hz, 2H),8.46(d,J = 5·61Ηz,2Η),8.28 (d,J = 8· 19Hz,2H),7.81 (m,3H),7.32 (d,J = 8·76Ηζ, 1H),6· 98(s,1H),6· 01 (s,2H),5· 60(s,2H),3· 96(s,3H),3· 81 (s,3H) ;13C 匪R(75MHz, DMS0-d6) δ :176. 81,157. 56,156. 12,150. 37,147. 77,144. 38,141. 57,132. 48,129. 85, 126. 85,124. 45,121. 08,113. 27,104. 83,63. 78,61. 12,60. 32,56. 32 ;MS-ESI
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