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一種四氫吲哚-4酮三肽類化合物,制備方法及其在抗腫瘤藥物中的用圖_3

文檔序號(hào):9919307閱讀:來源:國(guó)知局
,23.42,21.70,21.06,11.80.
[0061
[0062] N-(4-chlo;rophenyl )-2-(2-(2-methyl-4-〇x〇-4,5,6,7-tet;r 址 ydro-lH-indol-1-yl)-N-p-tolylacet amido)bu1:anamide(3d):怖ite solids,mp 222-224°C;1h NMR(400 MHz,CDCl3)S(wm):8.69-8.75(m,lH,NH),7.39-7.44(m,2H,2XCH),7.22-7.30(m,6H,6X CH),6.25(s,lH,CH),4.91-4.95(m,lH,=C-H),4.29-4.33(d,lH,C此),4.10-4.14(d,lH, CH2) ,2.50-2.52(m,2H,CH2) ,2.46-2.48(m,2H,C出),2.39-2.41(m,3H,CH3) ,2.02-2.04(m, 5H,-CH2(^3),1.64-1.71(m,2H,CH2),0.91-0.95(m,3H,(^3).i3CMffi(100MHz,CDCl3)5 (ppm):193.93,168.80,168.52,144.02,140.06,136.30,134.23,130.31,129.28,128.93, 120.90,119.97,103.66,62.00,46.19,37.55,23.45,21.99,21.80,21.14,11.81,10.79.
[0063:
[0064] N-(4-chlo;rophenyl )-2-(2-(2-methyl-4-〇x〇-4,5,6,7-tet;r 址 ydro-lH-indol-1-yl)-N-p-tolylacet amido)pentanamide(3e):化Ilow solids,mp 88_90°C;1h NMR(400 MHz,CDCl3)S(卵m):8.79(s,lH,NH),7.39-7.42(m,2H,2XCH),7.22-7.30(m,細(xì),6XCH), 6.25(s,lH,CH),5.01-5.04(m,lH,=C-H),4.29-4.33(d,lH, C此),4.09-4.14(d,lH,C此), 2.48-2.52(m,2H,C此),2,40-2,42(m,2H,C此),2.37-2.49(m,3H,CH3), 2.02-2.04(m,5H,-CH2C&),1.25-1.40(m,4H,2XCH2),0.85-0.88(m,3H,CH3).i3CMlR(100MHz,CDCl3)S (ppm):193.93,168.76,168.65,144.Ol,140.03,136.29,134.17,131.14,130.29,129.22, 128.91,128.49,120.87,119.91,103.60,60.27,46.18,37.53,30.64,23.43,21.77,21.15, 19.51,13.84,11.80.
[00 化]
[0066] N-(4-chIorophenyI)-N-(2-(4-chIorophenyIamino)-2-〇xoethyI )-2-(2-methyl-4-〇xo-4,5,6,7-t etrahydro-lH-indoI-1-yI)acetamide(3f):White solids,mp 249-25rC;iH 醒R(400 MHz,CDCl3)S(ppm):8.80(s,lH,NH),7.43-7.48(m,4H,4XCH), 7.35-7.37(m,2H,2XCH),7.17-7.19(m,2H,2XCH),6.17(s,lH,CH),4.33-4.35(m,4H,2X afe),2.54-2.57(m,2H,ai2),2.08(s,3H,ai3),2.02-2.06(m,2H,ai2).i3CMffi(100MHz, CDCl3)5(ppm):194.40,167.37,165.80,144.69,139.70,136.29,135.48,130.74,130.66, 129.36,129.20,128.88,121.11,119.90,103.64,54.34,45.61,37.57,23.48,21.81, 11.83.
[0067]
[0068] N-(4-chlo;ro 地 enyl )-2-(N-(4-chlo;ro 地 enyl )-2-(2-methyl-4-〇x〇-4,5,6,7-tetrahydro-lH-indol-1-yl)acetamido)butanamide(3g):White solids,mp 105-107°C ; Ih NMR(400 MHz,CDCl3)S(ppm):8.73(s,lH,NH),7.49(d,J = 8.9 Hz,3H,3XCH),7.36(d,J = 8.8 Hz,2H,2XCH),7.21(d,J = 8.8 Hz , 3H, 3 X CH), 6.25( s , 1H,CH) ,4.91(m, 1H,CH), 4.32(d,J=17.5Hz,lH,CH2),4.13(d,J=17.4Hz,lH,CH2),2.44-2.61(m,2H,CH2),2.30-2.44(m,2H,Ol2),2.04(d,J = 6.4Hz,5H,CH2CH3),1.64-1.68(m,lH,CH2),1.35-1.54(m,lH, CH2),0.92(m,3H,Ol3).i3CNMR(100MHz,CDCl3)S(wm):193.89,168.42,168.34,143.92, 136.01,135.95,135.46,130.61,130.21,129.39,128.89,120.92,120.00,103.74,62.12, 46.22,37.53,23.41,22.40,21.78,11.84,10.80.
[0化
[0070] 2-(N-benzy1-2-( 2-methyl-4-OXO-4,5,6,7-tetrahydr〇-lH-indol-1-yI) acetamido)-N-(4-chlo;rop henyl)butanamide(;3h):怖ite solids,mp 218-220°C;Ir NMR (400 MHz,CDCl3)S(卵m):8.73(s,lH,NH),7.33-7.43(m,7H,7XCH),7.22-7.31(m,2H,2X CH),6.25(s,lH,CH),4.94-4.97(m,lH,CH),4.82(s,2H,Ol2),4.46(s,2H,ai2),2.38-2.41 (m,4H,2XCH2),2.13-2.17(m,4H,2XCH2),1.95(s,3H,CH3),0.96-0.99(m,3H,CH3).i3c NMR (100 MHz,CDCb)S(ppm):194.02,169.59,168.14,144.19,136.22,136.14,130.51, 129.47,129.32,128.98,128.11,125.70,121.05,120.04,103.73,61.17,47.93,45.85, 37.54,23.44,21.77,21.50,11.82,10.69.
[0071:
[0072] N-(4-chlo;ro地enyl)-2-(N-(4-fluo;robenzyl)-2-(2-methyl-4-oxo-4,5,6,7-tetrahydr〇-lH-indol-1-yl)acetamido)butanamide(3i):Yellow solids,mp 143-145°C ;1h NMR(400 MHz,CDCl3)S(卵m):8.85(s,lH,NH),7.41-7.43(m,2H,2XCH),7.25-7.27(m, lH,CH),7.20-7.23(m,3H,3XCH),7.01-7.09(m,2H,2XCH),6.25(s,lH,CH),4.92-4.95(m, lH,CH),4.75(s,2H,Ol2),4.45(s,2H,CH2),2.38-2.43(m,4H,2XCH2),2.07-2.13(m,4H,2X C此),1.96(s,3H,CH3),0.96-0.99(m,3H,CH3).Uc 醒R(100 MHz,CDCl3)S(ppm):193.95, 169.48,168.08,163.57,161.11,144.12,136.10,131.99,130.44,129.63,129.05,127.54, 127.46,121.04,120.15,116.45,116.23,103.84,61.29,47.41,45.81,37.57,29.65, 23.46,21.83,21.61,11.83,10.68.
[0073
[0074」 N-H-chiorophenyi j-2-(N-(4-;t'iuo;robenzyl )-2-(2-methyl-4-0x0-4,5,6,7-tetrahydro-lH-indol-1-yl)acetamido)pentanamide(3j):White solids,mp 123-125°C ;1h NMR(400 MHz,CDCl3)S(卵m):8.85(s,lH,NH),7.41-7.43(m,2H,2XCH),7.20-7.27(m, 4H,4XCH),7.04-7.08(m,2H,2XCH),6.21(m,lH,CH),5.02-5.05(m,lH,CH),4.76(s,2H, C此),4.44(s,2H,afe),2.38-2.41(m,4H,2XCH2),2.01-2.36(m,4H,2XCH2),1.94(s,3H, (^3),1.31-1.41(m,2H,C&),0.91-0.95(m,3H,C&).i3CMlR(100MHz,CDCl3)S(ppm): 194.15,169.26,168.30,163.46,161.00,144.35,136.13,132.05,130.51,129.44,128.94, 127.49,127.41,121.02,119.9
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