Method for synthesizing 6H-benzo [5, 6] [1, 3] oxazino [3, 4-a] indole derivative by using allenoic acid ester

Abstract

The invention relates to synthesis of 6H-benzo [5, 6] [1, 3] oxazino [3, 4-a] indole derivatives, 2-(1H-indole-2-yl) phenol and derivatives thereof and allenoic acid esters including ethyl allenoate and benzyl allenoate are used as raw materials, the molar ratio of the raw materials to the raw materials is 1: 1, anhydrous sodium carbonate is used as a catalyst, the raw materials react in an acetonitrile solvent, and stirring reaction is performed at the temperature of 50 DEG C to generate a target product. The synthesis process route is simple, the dosage of the catalyst is only 10%, and the highest yield of the product reaches 98%.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and involves the synthesis of 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivatives by using inorganic base sodium carbonate (10%) as catalyst, 2-(1H-indole-2-yl)phenol and its derivatives and allenoic acid esters as raw materials, at 50°C, with the highest yield reaching 98%. Background Technology

[0002] The 6H-benzo[5,6][1,3]oxazin[3,4-a]indole structural unit is commonly found in many biologically active natural products and drug molecules. For example, the clinically used drug Elbasvir contains this core structure. This compound can be used in combination with grazoprevir to treat hepatitis virus C [Boyd, SD; Tracy, L.; Komatsu, TE; Harrington, PR; Viswanathan, P.; Murray, J.; Sherwat, A. Clin. Drug Invest. 2017, 37, 317.]. Due to the potential pharmaceutical applications of 6H-benzo[5,6][1,3]oxazin[3,4-a]indole compounds, the synthesis and structural modification of these compounds have become a hot topic in organic synthetic chemistry and medicinal chemistry research [(1)Xu,T.;Lin,N.;Hao,WJ;Zhang,J.;Li,MF;Tu,SJ;Jiang,B.,Chem.Commun.,2020,56,11406.(2)Hu,Y.;Wang,X.;Ren,N.;Li,N.;Li,J.Chen,J.;Zhang,H.;Deng,H.;Cao,W.;Lin,J.-H.,Eur.J.Org.Chem.2022,e202101501.]. In recent years, 2-(1H-indole-2-yl)phenol, as a versatile synthon, has also been used in the synthesis of 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivatives [Jia, P.; Huang, Y., Adv. Synth. Catal., 2018, 360, 3044.]. However, existing methods suffer from drawbacks such as the use of excess base as a catalyst and demanding reaction conditions. Furthermore, there are no reported methods for preparing 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivatives from 2-(1H-indole-2-yl)phenol and allenoate esters. Therefore, this invention relates to the preparation of 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivatives by reacting allenoate esters with substituted 2-(1H-indole-2-yl)phenol using anhydrous sodium carbonate as a catalyst at a catalytic concentration of only 10%. Summary of the Invention

[0003] The purpose of this invention is to provide an efficient method for synthesizing polysubstituted 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivatives: using 2-(1H-indole-2-yl)phenol and its derivatives and allenoic acid esters as raw materials, anhydrous Na2CO3 base as catalyst, acetonitrile as solvent, and stirring at 50°C to generate the target product (as shown in the attached figure).

[0004] This invention is achieved by the following method: 0.1 mmol of 2-(1H-indole-2-yl)phenol derivative (1), 0.1 mmol of allenoate (2), and 0.01 mmol of Na2CO3 were added to a 10 mL reaction tube equipped with a magnetic stir bar, followed by the addition of 1 mL of acetonitrile. The reaction tube was then sealed. The reaction was stirred at 50 °C, and the reaction was detected by thin-layer chromatography (TLC). After the reaction was completed, the reaction mixture was subjected to rotary evaporation under reduced pressure to obtain a crude product. Finally, the crude product was purified by silica gel column chromatography with ethyl acetate:petroleum ether = 1:15 (V:V) as the developing solvent to obtain the target product 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivative (3) (yield: 78%–98%).

[0005] The 2-(1H-indol-2-yl)phenol and its derivatives and allenoate esters are used as starting materials. The allenoate esters include ethyl allenoate and benzyl allenoate. The catalytic amount of Na2CO3 is 10%, the reaction solvent is acetonitrile, and the reaction temperature is 50℃.

[0006] The present invention has the following advantages:

[0007] In the synthesis of 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivatives, the catalytic amount of inorganic base Na2CO3 is only 10%. At the same time, allenoic acid esters and substituted 2-(1H-indole-2-yl)phenols with simple and readily available structures are selected as raw materials to explore a more efficient synthesis method. This method has the advantages of simple operation, convenient post-processing and high yield. Attached image description: Appendix Figure 1 Appendix Figure 1 This is a synthetic route diagram for the present invention. Detailed Implementation

[0008] The following is in conjunction with the appendix Figure 1 The present invention will be further described in conjunction with the embodiments.

[0009] Example 1:

[0010] Preparation of 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivative 3a: 0.1 mmol of 2-(1H-indole-2-yl)phenol, 0.1 mmol of benzyl allenoate, and 0.01 mmol of Na₂CO₃ were added to a 10 mL reaction tube equipped with a magnetic stir bar, followed by 2 mL of acetonitrile. The mixture was then sealed. The reaction was stirred at 50 °C for 15 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. Finally, the target product 3a was purified by silica gel column chromatography using ethyl acetate:petroleum ether = 1:15 (V:V).

[0011] Example 2:

[0012] Preparation of 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivative 3b: 0.1 mmol of 2-(-5-methoxy1H-indole-2-yl)phenol, 0.1 mmol of benzyl allenoate, and 0.01 mmol of Na₂CO₃ were added to a 10 mL reaction tube equipped with a magnetic stir bar, followed by 2 mL of acetonitrile. The mixture was then sealed. The reaction was stirred at 50 °C for 18 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. Finally, the target product 3b was purified by silica gel column chromatography using ethyl acetate:petroleum ether = 1:15 (V:V).

[0013] The reaction raw materials, reaction time and yield of Examples 1-16 are shown in Table 1.

[0014] Table 1. Reactants, reaction times, and yields for Examples 1-16

[0015]

[0016]

[0017] The characterization data of the obtained compounds are as follows.

[0018] Benzyl 2-(6-methyl-6H-benzo[5,6][1,3]oxazin[3,4-a]indol-6-yl)acetate (3a)

[0019] Colorless oil (35.9mg, 94% yield); 1H NMR(400MHz, CDCl3)δ(ppm)7.69(d,J=7.6Hz,1H),7.64(d,J=7.6Hz,1H),7.55(d,J=8.0Hz,1H),7.32(s,3H),7 .25-7.07(m,6H),6.96-6.87(m,2H),5.02(d,J=12.0Hz,1H),4.72(d,J=12.0Hz,1H),3.02(s,2H),2.43(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.3,148.2,135.2,134.5,131.7,129.8,129.2,128.4,128.3,128.2,12 3.6,122.9,122.4,120.9,120.5,117.8,117.5,111.5,97.8,89.3,66.7,43.6,26.2;IR(KBr)(v,cm -1 )1735,1467,1445,1389,1307,1235,1164,749,736,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 25 H 22 NO3 + 384.1594; Found 384.1594.

[0020] Benzyl 2-(10-methoxy-6-methyl-6H-benzo[5,6][1,3]oxazin[3,4-a]indol-6-yl)acetate (3b) Yellow oil (41.3 mg, 89% yield); 1 H NMR (400MHz, CDCl3) δ (ppm) 7.66 (d, J = 7.6Hz, 1H), 7.42 (d, J = 9.2Hz, 1H), 7.32 (s, 3H), 7.23-7.14 (m, 3H), 7.11-7.05 (m, 2H), 6. 91(d,J=8.4Hz,1H),6.86-6.78(m,2H),5.01(d,J=12.0Hz,1H),4.74(d,J=12.0Hz,1H),3.86(s,3H),2.98(s,2H),2.38(s,3H); 13 C{ 1H}NMR (100MHz, CDCl3) δ168.2,154.4,148.1,135.2,132.3,130.5,129.8,129.1,128.4,128.3,128.2 ,123.5,122.8,117.9,117.5,112.4,112.3,102.4,97.6,89.3,66.7,55.6,43.5,26.1; IR(KBr)(v,cm -1 )1734,1618,1459,1389,1298,1231,1164,1113,753,698; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 26 H 24 NO4 + 414.1700; Found 414.1702.

[0021] Benzyl 2-(6,10-dimethyl-6H-benzo[5,6][1,3]oxazinco[3,4-a]indol-6-yl)acetate (3c)

[0022] Colorless oil (31.1mg, 78% yield); 1 H NMR (400MHz, CDCl3) δ (ppm) 7.67 (d, J = 7.6Hz, 1H), 7.45-7.37 (m, 2H), 7.32 (s, 3H), 7.23-7.14 (m, 3H), 7.09 (t, J = 7.6Hz, 1H), 7.01 (d, J = 8.8H z,1H),6.91(d,J=7.6Hz,1H),6.81(s,1H),5.02(d,J=12.0Hz,1H),4.75(d,J=12.0Hz,1H),2.99(d,J=4.0Hz,2H),2.45(s,3H),2.39(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.3,148.2,135.3,132.9,131.7,130.1,129.8,129.0,128.4,128.3,128.2 ,124.0,123.51,122.8,120.7,117.8,117.6,111.2,97.4,89.3,66.7,43.5,26.1,21.2; IR(KBr)(v,cm -1)1733,1588,1456,1389,1309,1236,1164,1075,752,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 26 H 24 NO3 + 398.1751; Found 398.1755.

[0023] Benzyl 2-(10-fluoro-6-methyl-6H-benzo[5,6][1,3]oxazinco[3,4-a]indol-6-yl)acetate (3d)

[0024] Colorless oil (36.4mg, 91% yield); 1 H NMR(400MHz, CDCl3)δ7.65(d,J=7.6Hz,1H),7.42(dd,J=4.0,9.2Hz,1H),7.32(s,3H),7.27-7.20(m,2H),7.17-7.0 6(m,3H),6.95-6.87(m,2H),6.83(s,1H),4.99(d,J=12.0Hz,1H),4.72(d,J=12.0Hz,1H),2.99(s,2H),2.39(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.1,159.2,156.9,148.3,135.1,133.3,131.2,130.5,130.4,129.5,128.4,128.3,123.7 ,123.0,117.9,117.2,112.2,112.1,110.6,110.4,105.7,105.5,97.7,97.6,89.3,66.7,43.5,26.1; IR(KBr)(v,cm -1 )1733,1618,1589,1459,1390,1209,1159,956,753,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 25 H 21 FNO3 + 402.1500; Found 402.1488.

[0025] Benzyl 2-(10-chloro-6-methyl-6H-benzo[5,6][1,3]oxazinco[3,4-a]indol-6-yl)acetate (3e)

[0026] Colorless oil (40.1mg, 96% yield); 1 H NMR (400MHz, CDCl3) δ7.63(d,J=7.6Hz,1H),7.53(s,1H),7.39(d,J=8.8Hz,1H),7.29(s,3H),7.21(t,J=8.0Hz,1H),7.13- 7.03(m,4H),6.90(d,J=8.0Hz,1H),6.77(s,1H),4.96(d,J=12.0Hz,1H),4.70(d,J=12.0Hz,1H),2.96(s,2H),2.35(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.0,148.3,135.1,133.0,132.9,130.9,129.6,128.4,128.3,126.2 ,123.7,123.0,122.5,120.2,117.9,117.1,112.5,97.3,89.3,66.8,43.5,26.1; IR(KBr)(v,cm -1 )1734,1468,1446,1389,1317,1305,1248,1072,753,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 25 H 21 ClNO3 + 418.1204; Found 418.1205.

[0027] Benzyl 2-(10-bromo-6-methyl-6H-benzo[5,6][1,3]oxazinco[3,4-a]indol-6-yl)acetate (3f)

[0028] Colorless oil (41.6mg, 97% yield); 1 H NMR (400MHz, CDCl3) δ7.69(s,1H),7.63(d,J=7.6Hz,1H),7.35(d,J=8.8Hz,1H),7.29(s,3H),7.24-7.17(m,2H),7.13-7. 04(m,3H),6.90(d,J=8.4Hz,1H),6.76(s,1H),4.95(d,J=12.0Hz,1H),4.70(d,J=12.0Hz,1H),2.96(s,2H),2.34(s,3H); 13 C{1 H}NMR (100MHz, CDCl3) δ168.0,148.3,135.1,133.2,132.9,131.5,129.7,128.4,128.3,125.1 ,123.8,123.3,123.1,117.9,117.0,113.8,112.9,97.2,89.3,66.8,43.5,26.1; IR(KBr)(v,cm -1 )1733,1468,1444,1388,1317,1305,1232,784,753,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 25 H 21 BrNO3 + 462.0699; Found 462.0691.

[0029] Benzyl 2-(6,9-dimethyl-6H-benzo[5,6][1,3]oxazin[3,4-a]indol-6-yl)acetate (3g)

[0030] Colorless oil (37.8mg, 95% yield); 1 H NMR (400MHz, CDCl3) δ7.67(d,J=7.6Hz,1H),7.52(d,J=8.0Hz,1H),7.34(d,J=4.8Hz,4H),7.23-7.16(m,3H),7.09(t,J=7.2Hz,1H),6.99(d,J=8.0 Hz,1H),6.91(d,J=8.0Hz,1H),6.85(s,1H),5.05(d,J=12.4Hz,1H),4.79 (d,J=12.4Hz,1H),3.02(dd,J=13.6,24.0,2H),2.50(s,3H),2.41(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.3,148.0,135.3,135.0,132.3,131.10,128.8,128.4,128.3,128.2,127. 7,123.4,122.8,122.2,120.6,117.8,117.7,111.6,97.7,89.3,66.7,43.6,26.3,22.2;IR(KBr)(v,cm -1)1735,1588,1468,1387,1315,1234,1217,811,752,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 26 H 24 NO3 + 398.1751; Found 398.1751.

[0031] Benzyl 2-(9-chloro-6-methyl-6H-benzo[5,6][1,3]oxazinco[3,4-a]indol-6-yl)acetate (3h)

[0032] Colorless oil (40.9mg, 98% yield); 1 H NMR (400MHz, CDCl3) δ7.66(d,J=7.6Hz,1H),7.52(d,J=12.0Hz,2H),7.33(s,3H),7.25-7.16(m,3H),7.14-7.07(m,2H),6.9 2(d,J=8.0Hz,1H),6.84(s,1H),5.03(d,J=12.4Hz,1H),4.79(d,J=12.4Hz,1H),2.99(dd,J=13.6,19.2Hz,2H),2.37(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ167.9,148.2,135.2,134.8,132.5,129.5,128.4,128.3,128.3,128.1 ,123.6,123.0,121.6,121.2,117.9,117.2,111.5,97.8,89.3,66.8,43.5,26.1; IR(KBr)(v,cm -1 )1735,1468,1345,1307,1232,1154,931,813,753,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 25 H 21 ClNO3 + 418.1204; Found 418.1203.

[0033] Benzyl 2-(8-bromo-6-methyl-6H-benzo[5,6][1,3]oxazinco[3,4-a]indol-6-yl)acetate (3i)

[0034] Colorless oil (40.3mg, 87% yield); 1 H NMR (400MHz, CDCl3) δ7.70(d,J=7.6Hz,1H),7.65(d,J=8.0Hz,1H),7.56(d,J=8.4Hz,1H),7.32(s,3H),7.25 -7.07(m,5H),6.93(t,J=8.0,2H),5.02(d,J=12.0Hz,1H),4.72(d,J=12.0Hz,1H),3.02(s,2H),2.43(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.2,148.2,135.2,134.5,131.7,129.8,129.1,128.4,128.3,128.2,12 3.6,122.9,122.4,121.0,120.5,117.8,117.5,111.5,97.8,89.3,66.7,43.6,26.2;IR(KBr)(v,cm -1 )1735,1587,1467,1445,1389,1307,1234,748,735,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 25 H 21 BrNO3 + 462.0699; found 462.0686.

[0035] Benzyl 2-(11-chloro-6-methyl-6H-benzo[5,6][1,3]oxazinco[3,4-a]indol-6-yl)acetate (3j)

[0036] Colorless oil (38.3mg, 92% yield); 1 H NMR (400MHz, CDCl3) δ7.72(d,J=7.6Hz,1H),7.43(d,J=8.4Hz,1H),7.31(s,3H),7.23(d,J=7.6Hz,1H),7.17-7.05(m ,5H),7.00(s,1H),6.93(d,J=8.4Hz,1H),4.96(d,J=12.0Hz,1H),4.67(d,J=12.0Hz,1H),3.00(s,2H),2.40(s,3H); 13 C{ 1H}NMR (100MHz, CDCl3) δ168.1,148.2,135.1,135.0,132.3,129.7,128.6,128.4,128.3,126.2 ,123.9,123.1,122.8,120.3,117.9,117.1,110.2,96.3,89.4,66.9,43.6,26.1; IR(KBr)(v,cm -1 )1733,1485,1422,1389,1306,1244,1199,1144,753,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 25 H 21 ClNO3 + 418.1204; Found 418.1203.

[0037] Benzyl 2-(2-bromo-6-methyl-6H-benzo[5,6][1,3]oxazinco[3,4-a]indol-6-yl)acetate (3k)

[0038] Colorless oil (36.0mg, 78% yield); 1 H NMR (400MHz, CDCl3) δ7.76(s,1H),7.61(d,J=7.6Hz,1H),7.50(d,J=8.4Hz,1H),7.30(s,3H),7.24(d,J=8.4Hz,1H),7.21- 7.09(m,4H),6.85(s,1H),6.72(d,J=8.8Hz,1H),4.98(d,J=12.0Hz,1H),4.68(d,J=12,0Hz,1H),2.95(s,2H),2.36(s,3H); 13 C{ 1 H}NMR(100MHz, CDCl3)δ168.0,147.2,135.1,134.6,131.7,130.2,129.6,128.4,128.3(6),128.3(1) ,126.1,123.0,121.3,120.8,119.7,119.4,115.4,111.6,98.9,89.6,66.8,43.6,26.1; IR(KBr)(v,cm -1 )1733,1497,1388,1309,1235,1163,1075,1013,734,697; HRMS(APCI-TOF)m / z:[M+H] +Calcd for C 25 H 21 BrNO3 + 462.0699; Found 462.0697.

[0039] Benzyl 2-(1-methoxy-6-methyl-6H-benzo[5,6][1,3]oxazin[3,4-a]indol-6-yl)acetate (3l) Colorless oil (35.3mg, 85% yield); 1 H NMR (400MHz, CDCl3) δ7.66(d,J=8.0Hz,1H),7.55(d,J=8.0Hz,1H),7.32(s,4H),7.23-7.11(m,5H),6.68(d,J=8.4Hz,1H),6. 59(d,J=8.0Hz,1H),5.02(d,J=12.0Hz,1H),4.73(d,J=12.0Hz,1H),4.02(s,3H),2.99(dd,J=13.6,22.4Hz,2H),2.42(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.4,156.5,149.4,135.3,133.7,130.1,128.8,128.7,128.4,128.3,128.2 ,122.3,121.1,120.2,111.3,110.3,107.2,105.0,103.5,88.9,66.6,55.6,43.3,26.3; IR(KBr)(v,cm -1 )1735,1588,1487,1439,1309,1229,1092,799,732,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd forC 26 H 24 NO4 + 414.1700; Found 414.1702. Benzyl 2-(3,6-dimethyl-6H-benzo[5,6][1,3]oxazin[3,4-a]indol-6-yl)acetate (3m)

[0040] Colorless oil (37.8mg, 95% yield); 1H NMR (400MHz, CDCl3) δ7.63(d,J=7.6Hz,1H),7.61-7.51(m,2H),7.33(s,3H),7.23-7.11(m,4H),6.91(d,J=7.6Hz,1H),6.84( s,1H),6.74(s,1H),5.04(d,J=12.0Hz,1H),4.74(d,J=12.0Hz,1H),3.00(dd,J=13.6,20.0Hz,2H),2.41(s,3H),2.33(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.3,148.1,139.7,135.3,134.4,132.0,129.9,128.4,128.3,128.2,123.9 ,123.4,122.2,120.8,120.4,118.2,114.7,111.4,97.1,89.3,66.7,43.5,26.2,21.4; IR(KBr)(v,cm -1 )1733,1455,1389,1307,1265,1238,1167,784,734,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 26 H 24 NO3 + 398.1751; Found 398.1751.

[0041] Benzyl 2-(3-methoxy-6-methyl-6H-benzo[5,6][1,3]oxazin[3,4-a]indol-6-yl)acetate (3n) Colorless oil (36.6 mg, 89% yield); 1 H NMR (400MHz, CDCl3) δ7.64-7.56(m,2H),7.52(d,J=8.0Hz,1H),7.32(s,3H),7.22-7.09(m,4H),6.76(s,1H),6.68(d,J=8.4H z,1H),6.49(s,1H),5.04(d,J=12.0Hz,1H),4.74(d,J=12.0Hz,1H),3.76(s,3H),3.01(dd,J=13.6,22.4Hz,2H),2.41(s,3H); 13 C{ 1H}NMR(100MHz, CDCl3)δ168.3,160.8,149.5,135.3,134.3,132.0,130.1,128.4,128.2(4),128.2(0),12 4.6,121.9,120.6,120.4,111.3,110.4,110.2,102.5,96.2,89.5,66.7,55.4,43.5,26.2; IR(KBr)(v,cm -1 )1735,1625,1495,1439,1297,1271,1198,1158,733,697; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 26 H 24 NO4 + 414.1700; Found 414.1694.

[0042] Ethyl 2-(6-methyl-6H-benzo[5,6][1,3]oxazin[3,4-a]indol-6-yl)acetate (3o)

[0043] Colorless oil (31.4mg, 98% yield); 1 H NMR (400MHz, CDCl3) δ7.71(d,J=8.0Hz,1H),7.62(d,J=7.6Hz,1H),7.53(d,J=8.4Hz,1H),7.26(t,J=7.2Hz,1H),7.21-7.07(m, 3H),7.02(d,J=8.0Hz,1H),6.91(s,1H),4.00-3.89(m,1H),3.83-3.72(m,1H),2.94(s,2H),2.42(s,3H),0.99(t,J=8.0Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.4,148.3,134.6,131.7,129.8,129.2,123.6,122.9,122.4 ,120.9,120.4,117.8,117.6,111.6,97.8,89.4,60.8,43.7,26.2,13.7; IR(KBr)(v,cm -1 )1732,1588,1467,1445,1389,1306,1236,1031,749,736; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C20 H 20 NO3 + 322.1438; Found 322.14432.

[0044] Ethyl 2-(10-chloro-6-methyl-6H-benzo[5,6][1,3]oxazindo[3,4-a]indol-6-yl)acetate (3p)

[0045] White solid (33.4mg, 97% yield); mp 87-88℃; 1 H NMR (400MHz, CDCl3) δ7.65(d,J=8.0Hz,1H),7.53(s,1H),7.40(d,J=8.8Hz,1H),7.23(d,J=5.6Hz,1H),7.12-7.05(m,2H),6.98(d,J =8.0Hz,1H),6.79(s,1H),3.95-3.84(m,1H),3.79-3.69(m,1H),2.87(dd,J=13.2,21.2Hz,2H),2.36(s,3H),0.95(t,J=7.2Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ168.3,148.4,133.1,133.0,130.9,129.7,126.1,123.8,123.0 ,122.5,120.1,117.9,117.2,112.5,97.2,89.4,60.9,43.6,26.1,13.7; IR(KBr)(v,cm -1 )1732,1469,1446,1388,1318,1305,1233,1077,1031,754; HRMS(APCI-TOF)m / z:[M+H] + Calcd for C 20 H 19 ClNO3 + 356.1048; Found 356.1039.

Claims

1. This invention relates to the synthesis of a class of fused heterocyclic 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivatives, using 2-(1H-indole-2-yl)phenol and its derivatives and allenoic acid esters as raw materials, an inorganic base as a catalyst, reacting in an organic solvent, and stirring at an appropriate temperature to generate the target product.

2. The method for synthesizing the 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivative according to claim (1), characterized in that: The reaction raw materials for the synthesis are 2-(1H-indol-2-yl)phenol and its derivatives and allenoic acid esters, with a molar ratio of 1:

1. The suitable conditions are to use sodium carbonate as a base, react in acetonitrile solution, and generate the target product at 50°C.

3. The method for synthesizing the 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivative according to claim (1), characterized in that... The 2-(1H-indol-2-yl)phenol derivatives are substituted 2-(1H-indol-2-yl)phenols with electron-donating groups such as F, Cl, Br, etc., and electron-donating groups such as CH3, OCH3, etc., as starting materials.

4. The method for synthesizing the 6H-benzo[5,6][1,3]oxazin[3,4-a]indole derivative according to claim (1), characterized in that... The allenoic acid esters mentioned are ethyl allenoate and benzyl allenoate.

Images