双芳基烯烷酸类化合物及其制备方法和用图_5

文档序号:9518173阅读:来源:国知局
0. 48 (br, 1H),7. 95 化J= 8. 3Hz, 2H),7. 87 化J= 8. 4Hz, 2H),7. 79-7. 69 (m, 2H),7. 51 (dd,J= 10. 1,4. 9Hz, 2H),7. 48-7. 39 (m, 1H),7. 29-7. 25 (m, 2H),7. 24-7. 13 (m, 4H),7. 05 (d,J= 8.OHz, 2H),6. 59 (t,J= 5. 9Hz,IH),6. 17 (t,J =7. 4Hz,IH), 3. 03 (dd,J= 13. 2, 6. 7Hz, 2H), 2. 75-2. 63 (m, 2H), 2. 28 (t,J= 7. 4Hz, 2H),2. 15 (dd,J= 14. 8, 7. 4Hz, 2H),I. 92-1. 80 (m, 2H),I. 80-1. 69 (m, 2H);HRMS(EI) m/z计算C33H32ClN〇4S〇r)573. 1741,实测 573. 1741.
[051引 实施例91
[0513] 似-6-[4-巧-(2-蔡礙醜氨基)丙基]苯基]-6-(3-氯苯基)-5-己帰酸 (巧)-A30)的合成
[0514]
[051引将反应原料替换为中间体M46,操作同似-Al的制备。产率=92 %。古NMR(400MHz,丙丽-de) 5 10. 49 (br, 1H),8. 45 化J= 12. 9Hz, 1H),8. 18-8. 08 (m, 2H),8. 0 4 (d,J= 7. 7Hz, 1H),7. 89 (dd,J= 8. 7, 1. 8Hz, 1H),7. 69 (tt,J= 12. 7, 3. 5Hz, 2H),7. 34 -7. 23 (m, 2H),7. 20 (t,J=I. 6Hz,IH),7. 17-7. 08 (m, 3H),7. 05-6. 95 (m, 2H),6. 64 (t,J= 5. 8Hz,IH),6. 17 (t,J= 7. 4Hz,IH),3. 02 (dd,J= 13. 1,6.細z, 2H),2. 71-2. 61 (m, 2H),2. 2 9(t,J= 7. 4Hz, 2H), 2. 14(dd,J= 14. 8, 7. 4Hz, 2H),I. 87-1. 71(m,4H)巧觀8巧0111八计算 C3iH30ClN04S0r)547. 1584,实测 547. 1579.
[0516] 实施例92
[0517] 似-6-[4-巧-(5-二甲氨基-I-蔡礙醜氨基)丙基]苯基]-6-(3-氯苯基)-5-己 帰酸(巧)-A31)的合成
[051 引
[0519] 将反应原料替换为中间体M47,操作同似-Al的制备。产率=89 %。Ih NMR(400MHz,丙丽-de) 5 10. 49 (br, 1H),8. 56 化J= 8. 6Hz, 1H),8. 45 化J= 8. 7Hz, 1田,8. 26-8. 18 (m, 1田,7. 60 (dd,J= 15.8, 7. 4Hz, 2H),7. 33-7. 22 (m, 3H),7. 21-7. 09 (m, 2田,7. 05-6. 90 (m, 4H),6. 80 (t,J=6.OHz, 1田,6. 17 (t,J= 7. 4Hz, 1田,2. 98 (dd,J =12.8,6.6Hz, 2H),2. 87 (S,6H),2. 56-2. 47 (m, 2H),2. 29 (t,J= 7. 4Hz, 2H),2. 14 (dd,J =14. 9, 7. 4Hz, 2H),I. 72 (dq,J= 22. 2, 7.IHz, 4H);HRMS(EI)m/z计算 C33H35CIN2O4Sor) 590. 2006,实测 590. 2004.
[0520] 实施例93
[0521] 似-6-[4-巧-(哇晰-8-礙醜氨基)丙基]苯基]-6-(3-氯苯基)-5-己帰酸 (巧)-A32)的合成
[0522]
[052引将反应原料替换为中间体M48,操作同似-Al的制备。产率=87%。古NMR (400MHz,丙丽-de)5 10. 48化r, 1H),9. 11-9. 06 (m, 1H),8. 56-8. 53 (m, 1H),8. 44-8. 34 (m ,1H),8. 30-8. 27 (m, 1H),7. 85-7.66(m, 2H),7. 50-7. :34 (m, 1H),7. 34-7. 17 (m, 2H),7. 14-6. 9 5 (m, 5H),6. 78 (dd, J = 12. 7,6.甜Z, 1H),6. 14 (化,J = 22. 7, 7.甜Z, 1H),2. 92 (dd, J = 13. 2 ,6. 7Hz, 2H),2. 65-2. 49 (m, 2H),2. 29 (dd, J = 10. 4, 4. 4Hz, 2H),2. 13 (m, 2H),1. 88-1. 64 (m, 4H) ;HRMS巧I)m/z计算C30H29ClN204S0r)548.1537,实测548. 1535.
[0524] 实施例94
[0525] 巧)-6-[4-[2-[4-(4-氣苯基)苯礙醜氨基]己基]苯基]-6-(3-氯苯基)-5-己 帰酸(巧)-A33)的合成
[0526]
[0527]将反应原料替换为中间体M49,操作同似-Al的制备。产率=87 %。Ih NMR(400MHz,丙丽-de) 5 10. 48(br,lH),7. 95(d,J=8.甜z,2H),7.86(d,J= 8.4H z, 2H),7. 82-7. 75 (m, 2H),7. 35-7. 13 (m,細),7. 08 (d, J =8. OHz, 2H),6. 64 (t, J = 5. 9Hz, IH),6. 19(t, J = 7. 4Hz, IH), 3. 27(dd, J = 13.8, 7. 2Hz, 2H),2.88(d, J = 7.8Hz, 2H),2. 29 (t, J = 7. 4Hz, 2H),2. 16 (dd, J = 14.8, 7. 4Hz, 2H),I. 79-1. 72 (m, 2H); HRMS巧I)m/z计算C3化9C1FN04S(]T)577. 1490,实测577. 1491.
[052引 实施例95
[0529] 巧/Z) -6- [4- [2- [4- (4-氯苯基)苯礙醜氨基]己基]苯基]-6- (3-氯苯基)-5-己 帰酸((E/幻-A34)的合成
[0530] 将反应原料替换为中间体M50,操作同似-Al的制备。
[0531]
[053引 产率=79 %。古NMR(400MHz,丙丽-de) 5 10. 48(br,1H),7. 96 化J= 8.甜Z, 2田,7. 88 (d,J= 8. 5Hz, 2H),7. 80-7. 70 (m, 2H),7. 60-7. 49 (m, 2H),7. 33-7. 19 (m, 5H),7. 16 (d,J= 7. 4Hz, 1H),7. 08 (d,J= 8.OHz, 2H),6. 66 (t,J= 5. 9Hz, 1H),6. 19 扣J =7.4Hz,lH),3. 27(dd,J= 13. 8,7. 2Hz,2H),2.88(d,J= 7. 9Hz,2H),2. 29(t,J= 7. 4Hz, 2H),2. 16 (dd,J=14.8,7. 4Hz, 2H),I. 75 (p,J=7. 4Hz, 2H) ;HRMS巧I)m/z计算 C32H29Cl2N04S0r)593.1194,实测593. 1192.
[0533]
[0534] 产率=11%。咱NMR(400MHz,丙丽-de) 5 7. 88(dd,J= 21.3,8. 4Hz,4H),7. 76(d,J =8. 6Hz, 2H),7. 55 (d,J= 8. 6Hz, 2H),7. 49-7. 33 (m, 2H),7. 22-7. 00 (m, 6H),6. 61 (t,J= 5. 8Hz,IH),6. 14 (t,J= 7. 5Hz,IH),3. 21 (dd,J= 14. 0, 7.IHz, 2H),2. 82-2. 77 (m, 2H),2. 2 9 (t,J= 7. 3Hz, 2H),2. 14 (dd,J= 14. 8, 7. 4Hz, 2H),I. 80-1. 70 (m, 2H);HRMS(ESI)m/z计算 CszHzsCIzNOaSDm-田592.i。2,实测592.ms.
[0535] 实施例96
[0536] 巧/Z)-6-[4-[2-[4-(4-甲基苯基)苯礙醜氨基]己基]苯基]-6-(3-氯苯 基)-5-己帰酸((E/幻-A35)的合成
[0537] 将反应原料替换为中间体M51,操作同似-Al的制备。
[053引
[0539]产率=76 %。古NMR(400MHz,丙丽-de) 5 10. 47(br,1H),7.93化J= 8.5Hz, 2H),7. 85 (d,J= 8.4Hz, 2H),7. 62 (d,J= 8.IHz, 2H),7. 36-7. 28 (m, 3H),7. 27-7.22 (m,4H),7. 16(dd,J = 7. 4,1.5Hz,lH),7. 08(d,J =8. 0Hz,2H),6.61(t,J =6. OHz, IH),6. 18(t, J = 7. 4Hz, IH), 3. 26(dd, J = 13.8, 7. 3Hz, 2H), 2.88(d, J =7. 7Hz, 2H),2. 39 (s, 3H),2. 29 (t, J = 7 . 4 H z,2 H),2 . I6( d d,J = 14.8, 7. 4Hz, 2H), I. 80-1. 71 (m, 2H)巧觀8巧〇111八计算C33H32ClN〇4S〇r)573. 1741,实测J 573. 1743.
[0540]
[0541]产率=9%。电NMR(400MHz,丙丽-de) 5 7. 85(dd,J = 22. 9,8. 4Hz,4H),7. 63(d,J =8. IHz, 2H),7. 48-7. 28 (m, 4H),7. 23-7. Ol (m,6H),6. 56 (t, J = 5.8Hz, IH),6. 14 (t, J = 7. 4Hz, IH),3. 20 (dd, J = 14. 0, 7. OHz, 2H),2. 81-2. 78 (m, 2H),2. 39 (s, 3H),2. 29 (t, J = 7. 4Hz, 2H),2. 14 (dd, J = 14. 9, 7. 4Hz, 2H),I. 75 (dd, J = 14. 9, 7. 5Hz, 2H) ;HRMS (ESI) m/z 计算C33H3iC1N〇4S[M-田572. 1668,实测572. 1661.
[0542]实施例97
[054引巧)-6-[4-[2-[4-(4-甲氧基苯基)苯礙醜氨基]己基]苯基]-6-(3-氯苯 基)-5-己帰酸(巧)-A36)的合成
[0544]
[0545]将反应原料替换为中间体M52,操作同似-Al的制备。产率=88%。 古醒尺(4001化,丙丽-(16)5 10.50化',1出,7.92((1,1 = 8.6化,2出,7.84((1,1 = 8. 6Hz, 2H),7. 70化J =8. 9Hz, 2H),7. 31-7. 23 (m, 5H),7. 19-7. 16 (m, 1H),7. 13-7. 02 (m, 4H ),6. 61 (t, J = 5. 9Hz, IH),6. 20 (t, J = 7. 4Hz, IH), 3. 87 (s, 3H), 3. 34-3. 20 (m, 2H), 2. 89 (d, J = 7.細z, 2H),2. 30 (t, J = 7. 4Hz, 2H),2. 18 (dd, J = 14. 9, 7. 4Hz, 2H),I. 82-1. 74 (m, 2H); HRMS(ESI)m/z计算C33H3iC1N〇sS[M-田588. 1617,实测588. 1607.
[0546]实施例98
[0547]似-6-[4-巧-(3-硝基苯礙醜氨基)己基]苯基]-6-(3-漠苯基)-5-己帰酸 (巧)-A37)的合成
[054引
[0549] 将反应原料替换为中间体M53,操作同似-Al的制备。产率=86 %。古 醒R(400MHz,丙丽-屯)5 8. 02-7. 93 (m, 2H),7. 46-7. 32 (m, 5H),7. 27-7. 22 (m, 3H),7. 10(d,J= 8. 0Hz,2H),6. 67(t,J= 5.細z,lH),6. 19(t,J= 7. 4Hz,lH),3. 24(dd,J= 14. 5,6. 7Hz,2H),2. 86(t,J= 7. 6Hz,2H),2. 31(dd,J= 9. 6,5.lHz,2H),2. 18(dd,J= 14.8,7.4化,2巧,1.81-1.73(111,2巧巧觀5巧5〇111八计算〔2(品48'肥〇65[]\1-田 571.0544,实 测 571. 0574.
[0巧0] 实施例99
[0巧1 ] 胆)-6- [4-巧-(4-H氣甲基苯礙醜氨基)己基]苯基]-6- (3-漠苯基)-5-己帰酸 (巧)-A38)的合成
[0巧2]
[0巧3] 将反应原料替换为中间体M54,操作同似-Al的制备。产率=83 %。古 NMR(400MHz,丙丽-de) 5 8. 12(d,J= 8. 2Hz,2H),7. 97(d,J= 8. 3Hz,2H),7. 41(dd,J=9. 9,4. 5Hz,2H),7. 23(dd,J= 13. 1,6. 8Hz,4H),7. 15-7.08(m,2H),6. 90(t,J= 5. 7Hz,lH),6. 19(t,J= 7. 5Hz,lH),3. 30(dd,J= 13. 9,7. 0Hz,2H),2. 88(t,J= 7. 5H z,2H),2. 37-2. 26 (m,2H) ,2.24-2. 12 (m,2H) ,1.82-1. 73 (m,2H);HRMS(ESI)m/z计算 C27H24BrF3N〇4S[M-田 594. 0567,实iU594. 0549.
[0巧4] 实施例100
[0巧5] 似-6- [4-巧-(4-氯苯礙醜氨基)丙基]苯基]-6- (3-漠苯基)-5-己帰酸 (巧)-A39)的合成
[0巧6]
[0巧7] 将反应原料替换为中间体M55,操作同似-Al的制备。产率=88 %。Ih NMR(400MHz,丙丽-de) 5 7. 89 化J= 8. 6Hz, 2H),7. 65 化J= 8. 5Hz, 2H),7. 44-7. 39 (m, 2H),7. 29-7. 17 (m, 4H),7. 10 (dd,J= 13. 1,6. 3Hz, 2H),6. 68 (t,J= 5. 5Hz, 1H),6. 19 扣J =7. 4Hz,IH), 3.Ol(dd,J= 13. 2, 6. 7Hz, 2H), 2. 75-2. 64 (m, 2H), 2. 31 (dd,J= 8. 7, 6.IHz, 2H),2. 18(dd,J= 14. 8, 7. 4Hz, 2H),I. 91-1. 81(m,2H),I. 77(dd,J= 14. 7, 7. 4Hz, 2H) ;HRMS(ESI)m/z计算C27H2eBrClN〇4S[M-田 574. 0460,实测 574. 0446.
[0巧引 实施例101
[0巧9] 似-6- [4-巧-(4-氣苯礙醜氨基)丙基]苯基]-6- (3-漠苯基)-5-己帰酸 (巧)-A40)的合成
[0560]
[0561] 将反应原料替换为中间体M56,操作同似-Al的制备。产率=84%。古 NMR (400MHz,丙丽-de) 5 7. 99-7. 90 (m, 2H),7. 45-7. 31 (m, 5H),7. 25-7. 19 (m, 3H),7. 10 (dd,J = 12. 3,5. lHz,2H),6. 62(t,J = 5. 7Hz,lH),6. 18(t,J = 7. 4Hz,lH),3. 00(dd,J =13. 1,6.細z,2H),2. 74-2.64(m,2H),2. 31(dd,J =8.8,6. 0Hz,2H),2. 18(dd,J = 14.8, 7. 4Hz, 2H),I.86(dt, J = 14. 4, 7. OHz, 2H),I. 77 (dd, J = 14. 7, 7. 4Hz, 2H) ;HRMS (ESI) m/z计算C27H26化FN04S[M-田558. 0755,实测558. 0731.
[0562] 实施例102
[0563] 巧)-6-[4-巧-(4-H氣甲基苯礙醜氨基)丙基]苯基]-6-(3-漠苯基)-5-己帰酸 (似-A41)的合成
[0564]
[056引将反应原料替换为中间体M57,操作同似-Al的制备。产率=81 %。Ih NMR (400MHz,丙丽-de) 5 8.12 (d, J = 8.2Hz, 2H), 7.97 (d, J = 7. 2Hz,2H),7. 39(s,2H),7. 20(d,J =8. 3Hz,4H),7. 09(t,J = 7. 9Hz,2H),6.86(t,J =5. 5Hz, IH),6. 18(t, J = 7. 4Hz, IH), 3. 06(dd, J = 12. 9,6. 5Hz, 2H),2. 69 (t, J = 7.甜z, 2H),2. 31 (t, J = 7. 3Hz, 2H),2. 18 (dd, J = 14. 7, 7. 3Hz, 2H),I. 92-1. 83 (m, 2H), I. 78(化,J=14.6, 7. 2Hz, 2H) ;HRMS(ESI)m/z计算[28?出rF3N04S[M-田608. 0723,实测 608. 0710.
[0566] 实施例103
[0567] 巧)-6-[4-巧-(4-叔了基苯礙醜氨基)丙基]苯基]-6-(3-漠苯基)-5-己帰酸 (巧)-A42)的合成
[0568]
[0569]将反应原料替换为中间体M58,操作同似-Al的制备。产率=87%。古 醒尺(4001化,丙丽-(16) 5 7.78扣1 = 9.6化,2出,7.64((1,1 = 8.3化,2巧,7.45- 7. 35(m,2H),7. 21(dd,J = 20. 2,7. 5Hz,4H),7. 06(d,J = 7. 9Hz,2H),6. 48(t,J = 5.8Hz, IH),6. 18 (t, J = 7. 4Hz, IH),2. 97 (dd, J = 13.6,6.細z, 2H),2. 72-2. 62 (m, 2H),2. 3 0(t, J = 7. 4Hz, 2H), 2. 23-2. 12(m, 2H), I. 88-1. 69(m,4H), I. 35(s,9H) ;HRMS(ESI)m/z计算 C31H35化N04S[M-田5%. 1476,实测596. 1458.
[0570]实施例104
[0571] (E/幻-6- [4-巧-(4-叔戊基苯礙醜氨基)己基]苯基]-6- (3-漠苯基)-5-己帰酸 ((E/幻-A43)的合成
[057引将反应原料替换为中间体M59,操作同似-Al的制备。
[0573]
[0574] 产率=81%。电NMR(400MHz,丙丽-de) 5 7. 80化J =8. 5Hz,2H),7. 58化J = 8. 5Hz, 2H),7. 44-7. 36 (m, 2H),7. 22 (t, J =8. 3Hz, 4H),7. 08化J =8. OHz, 2H),6. 49 (t, J =5.8Hz, 1H),6. 18 (t, J = 7. 5Hz, 1H),3. 28-3. 16 (m, 2H),2. 86-2. 81 (m, 2H),2. 29 (t, J = 7. 4Hz,2H),2. 22-2. ll(m,2H),1.82-1.64(m,4H),1.31(s,細),1.20(t, J = 7. lHz,3H); HRMS (EI) m/z计算C3i&出rN〇4S or) 597. 1548/599. 1528,实测599. 1532.
[0575]
[057引产率=13%。咱NMR(400MHz,丙丽-de)5 10. 4^br, 1H),7. 7^d, J=8.甜z,2H ),7. 62-7. 49 (m, 3H),7. 37 (dd, J = 20.8, 13. OHz, 2H),7. 19 (d, J = 7. 7Hz, IH),7. 10 (q, J = 8. 3Hz, 4H),6. 44 (t, J = 5. 9Hz, IH),6. 16 (t, J = 7. 4Hz, IH),3. 15 (dd, J = 13. 9, 7. IHz, 2 H),2. 79-2. 74 (m, 2H),2. 30 (t, J = 7. 4Hz, 2H),2. 15 (dd, J = 14.8, 7. 4Hz, 2H),I. 73 (dq, J =28. 3,7. 4Hz,4H),1.31(s,6H),0.65(t,J = 7.4Hz,3H) ;HRMS(EI)m/z计算 〔3化6化N04S(]T)597. 1548,实测597. 1545.
[0577] 实施例105
[057引 (E/幻-6- [4-巧-(4-环己基苯礙醜氨基)己基]苯基]-6- (3-漠苯基)-5-己帰酸 (巧/幻-A44)的合成
[0579] 将反应原料替换为中间体M60,操作同似-Al的制备。
[0580]
[05引]产率=84 %。电NMR(400MHz,丙丽-de) 5 10. 45 化r, 1H), 7. 78化J= 8. 2H z,2H),7. 50-7. 35 (m,4H), 7.22 (t,J= 8.4Hz, 4H), 7.07 (d,J= 7.9Hz, 2H), 6.47 (t,J =5.細z,lH),6. 18(t,J= 7. 5Hz,lH),3. 21(dd,J= 14. 0,7. 0Hz,2H),2. 83(d,J =7.4Hz,2H),2.63(t,J= 10.lHz,lH),2. 29(t,J= 7.4Hz,2H),2. 17(dd,J= 14. 8, 7. 4Hz, 2H),I. 82 (d,J= 19. 2Hz, 4H),I. 75 (dd,J= 14. 7, 7. 3Hz, 3H),I. 47 (化,J =22. 5, 12.OHz, 4H),I. 29 (dd,J= 10. 3, 4. 4Hz,IH) ;HRMS(EI)m/z计算 〇32&6化N〇4S〇r)609. 1548,实测 609. 1528.
[0582]
[058引 产率=16 %。Ih醒R(400MHz,丙丽-屯)5 10. 41Ar, 1田,7. 74 (d,J =8. 2Hz, 2H),7. 53 (d,J= 7. 9Hz, 1H),7. 45-7. 36 (m, 3H),7. 32(S,1H),7. 19 (d,J= 7. 8Hz,IH), 7. 09 (q,J= 8. 3Hz, 4H), 6. 42 (t,J= 5. 8Hz,IH), 6. 16 (t,J =7. 4Hz,IH), 3. 14(dd,J= 13. 9, 6. 9Hz, 2H), 2. 78-2. 74 (m, 2H), 2. 64 (d,J= 8. 8Hz,IH),2. 30 (t,J= 7. 4Hz, 2H),2. 16 (dd,J= 14. 8, 7. 4Hz, 2H),I. 84 (d,J= 8.IHz, 4H ),I. 80-1. 73 (m, 3H),I. 52-1. 40 (m, 5H)巧RMS巧0111八计算C32&击rN04Sor) 609. 1548,实测 609. 1526.
[0584] 实施例106
[0585] (E/幻-6-[4-巧-(4-苯基苯礙醜氨基)己基]苯基]-6-(3-漠苯基)-5-己帰酸 ((E/幻-A45)的合成
[0586] 将反应原料替换为中间体M61,操作同似-Al的制备。
[0587]
[058引产率=85%。古NMR (400MHz,丙丽-de) 5 10. 44(s,1H),7. 95化J = 8. 4Hz,2H), 7.87 (d, J = 8.3Hz, 2H), 7.73 (d, J = 7.3Hz, 2H), 7.51 (t, J = 7.4Hz,2H),7. 47-7. 35 (m, 3H),7. 28-7. 16 (m, 4H),7. 08 (d, J =8. OHz, 2H),6. 61 (t, J = 6. OHz, IH),6. 17 (t, J = 7. 4Hz, IH),3. 28 (dd, J = 14. 0, 7. IHz, 2H),2. 93-2. 85 (m, 2H),2. 2 9(t, J = 7. 4Hz,2H),2. 17(dd, J = 14. 8,7. 4Hz,2H), 1.82-1.68(m,2H) ;HRMS巧I)m/z计算 C32H30BrN04S0r)605. 1058,实测603. 1049.
[0589]
[0590] 产率=14 %。古NMR (400MHz,丙丽-de)5 7. 87(dd,J=23. 3,8. 4Hz ,3H), 7. 75-7. 67 (m, 3H), 7. 64-7. 50 (m, 5H), 7. 44(t, J = 7. 3Hz, IH), 7. 37(t, J =7.8Hz, IH), 7. 30(s,IH), 7. 16(d,J = 7. 7Hz, IH), 7. 11(s,2H),6. 57 (t, J = 6. 3Hz, IH),6. 14 (t, J = 7. 5Hz, IH),3. 21 (dd, J = 13. 9, 7. OHz, 2H),2. 80-2. 78 (m, 2H),2 ,29(t,J = 7. 4Hz,2H),2. 14(dd,J = 14. 9,7. 5Hz,2H),l. 76(dd,J = 14. 8,7. 5Hz,2H); 11觀5巧51)111八计算〔32&9化側45[]\1-田604.0980,实测604.0984.
[0591]实施例107
[0592] (E/幻-6- [4-巧-(2-蔡礙醜氨基)己基]苯基]-6- (3-漠苯基)-5-己帰酸((E/ 幻-A46)的合成
[059引将反应原料替换为中间体M62,操作同似-Al的制备。
[0594]
[059引 产率=86 %。IhNMR(400MHz,丙丽-de) 5 8. 49 (s, 1H),8. 13 (dd,J= 12. 1,8. 4Hz, 2H),8. 03 (d,J= 7.細z,lH),7.89(d,J= 8.6Hz,lH),7.74-7.64(m,2H),7.44- 7. :M (m, 2H),7. 27-7. 14 (m, 4H),7. 05 (d, J = 7.8Hz, 2H),6.68(t, J =6. OHz, IH),6. 16扣J =7. 4Hz, IH), 3. 26 (dd, J = 14. 3,6. 9Hz, 2H), 2. 88-2. 83 (m, 2H), 2. 28 (t, J = 7. 4Hz, 2H), 2. 14(dt, J = 11. 1,5.甜Z, 2H), I. 79-1. 69(m, 2H)巧RMS巧I)m/z计算CsoHzsBrNO4S or) 577. 0922/577. 0902,实测579. 0901.
[0596]
[0597]产率=15%。古NMR(400MHz,丙丽-de) 58. 44(s, 1H),8. 16-8. 01(m,3H ),7. 83 (d, J =8. 7Hz, IH),7. 70 (dd, J = 13. 5,6. 7Hz, 3H),7. 57-7. 49 (m, 2H),7. 37 (t,J = 7.細z,lH),7. 30(s,lH),7. 17(d,J = 7. 5Hz,lH),7.07(s,3H),6. 62(t,J = 5. 9Hz, IH),6. 12 (t, J = 7. 5Hz, IH),3. 21 (dd, J = 14. 0,6. 9Hz, 2H),2. 80-2. 75 (m, 2H),2. 3 O (t, J = 7. 3Hz, 2H),2. 14 (dd, J = 14.8, 7.甜z, 2H),I. 79-1. 72 (m, 2H) ;HRMS巧〇m/z计算 〇3。&击rN〇4S or) 577. 0922,实测577. 0923.
[059引实施例108
[0599] (E/口-6- [4-巧-(5-二甲氨基-I-蔡礙醜氨基)己基]苯基]-6- (3-漠苯 基)-5-己帰酸((E/幻-A47)的合成
[0600] 将反应原料替换为中间体M63,操作同似-Al的制备。
[0601]
[060引产率=83 %。Ih NMR (400MHz,丙丽-de) 5 10. 40 (br, 1H), 8.58化J = 8. 6Hz, 1H),8. 39 (d, J =8. 7Hz, 1H),8. 26 (dd, J = 7. 3, 0. 9Hz, 1H),7. 70-7. 60 (m ,IH),7. 59-7. 52 (m, IH),7. 38 (dd, J = 17. 2, 4. 7Hz, 2H),7. 30-7. 14 (m, 3H),7. 07 ( d, J =8. OHz, 2H),6. 9
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