Pyran[2,3-b] quinoline derivative as well as synthesis process and application thereof in tumor prevention

A synthetic process, 3-b technology, applied in the direction of antineoplastic drugs, drug combination, organic chemistry, etc., can solve the problem that synthetic raw materials are not easy to obtain, and achieve a good effect of inhibiting proliferation in vitro

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A synthetic process, 3-b technology, applied in the direction of antineoplastic drugs, drug combination, organic chemistry, etc., can solve the problem that synthetic raw materials are not easy to obtain, and achieve a good effect of inhibiting proliferation in vitro

CN108218883AActive Publication Date: 2018-06-29JINGHUA PHARMA GRP NANTONG

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Embodiment 1

[0033] Add 2-chloroquinoline-3-carbaldehyde (0.2mmol), malononitrile (0.2mmol) and 4-hydroxycoumarin (0.2mmol) into a 5mL microwave reaction tube, then add L-proline (0.1mmol ) and 2 mL of ethanol, seal the reaction tube, stir for 10 seconds in advance, and react the mixture at 100°C for 30 minutes under microwave radiation. A mixed solvent of water was recrystallized to obtain 2-(6-oxo-6,7-dihydrochromeno[3',4':5,6]pyrano[2,3-b]quinoline-7 -yl) malononitrile (Ia): Yield 71%; m.p.:274-276°C; IR(KBr,ν,cm -1 ):2917,2250,1701,1638,1607,1493,1404,1332,1244,1204,1169,1151,1050,1025,987,769,754; 1 H NMR (400MHz, DMSO-d 6 )(δ,ppm):8.84(s,1H,ArH),8.15(d,J=8.0Hz,2H,ArH),8.04(d,J=8.4Hz,1H,ArH),7.94-7.90(m, 1H, ArH), 7.86-7.82(m, 1H, ArH), 7.70(t, J=7.6Hz, 1H, ArH), 7.61(d, J=8.4Hz, 1H, ArH), 7.57(t, J= 8.0Hz, 1H, ArH), 5.38(d, J=4.0Hz, 1H, CH), 5.34(d, J=3.6Hz, 1H, CH). 13 C NMR (100MHz, DMSO-d 6 )(δ,ppm):162.3,160.0,158.5,153.7,152.6,145.6,140.8,134.0,131.9,128.3,127.6,127.0,12...

Embodiment 2

[0035] According to the method for embodiment 1, 2-chloroquinoline-3-formaldehyde is changed into 6-methoxyl group-2-chloroquinoline-3-formaldehyde, with L-proline as catalyst, reacted under microwave radiation for 30 minutes, After the reaction, the reaction system was cooled to room temperature, and after the solid was precipitated, suction filtration was performed, and the target product 2-(10-methoxy-6-oxo-6,7-di Hydrochromeno[3',4':5,6]pyrano[2,3-b]quinolin-7-yl)malononitrile (Ib): Yield 75%; m.p.:258-260°C; IR(KBr,ν,cm -1 ):2903,2254,1686,1637,1609,1497,1455,1353,1236,1172,1113,1025,1005,993,794,747; 1 H NMR (400MHz, DMSO-d 6 )(δ,ppm):8.69(s,1H,ArH),8.14-8.11(m,1H,ArH),7.94(d,J=9.2Hz,1H,ArH),7.85-7.81(m,1H,ArH ),7.61-7.53(m,4H,ArH),5.35(d,J=3.6Hz,1H,CH),5.31(d,J=3.6Hz,1H,CH),3.94(s,3H,CH 3 O). 13 C NMR (75MHz, DMSO-d 6 )(δ,ppm):160.5,159.0,158.1,153.1,152.6,141.7,139.6,134.4,129.5,128.6,125.7,124.9,123.4,117.4,113.7,113.6,113.2,112.9,106.4,67.7 , 30.8. HRMS Calcd...

Embodiment 3

[0037] According to the method for Example 1, 2-chloroquinoline-3-formaldehyde is replaced with 6-tert-butyl-2-chloroquinoline-3-formaldehyde, and L-proline is used as a catalyst to react under microwave radiation for 30 minutes, After the reaction, the reaction system was cooled to room temperature, and after the solid was precipitated, suction filtration was performed, and the target product 2-(10-tert-butyl-6-oxo-6,7-di Hydrochromeno[3',4':5,6]pyrano[2,3-b]quinolin-7-yl)malononitrile (Ic): Yield 73%; m.p.: 284-286°C; IR(KBr, ν, cm -1 ):2963,2255,1702,1640,1610,1497,1460,1438,1396,1380,1366,1271,1183,1169,1150,1126,1098,988,969,915,831; 1 H NMR (400MHz, DMSO-d 6 )(δ,ppm):8.82(s,1H,ArH),8.17(d,J=7.6Hz,1H,ArH),8.09-8.00(m,3H,ArH),7.86(t,J=8.0Hz, 1H, ArH), 7.64-7.58(m, 2H, ArH), 5.38(d, J=3.6Hz, 1H, CH), 5.34(d, J=3.6Hz, 1H, CH), 1.45(s, 9H, (CH 3 ) 3 C). 13 C NMR (75MHz, DMSO-d 6 )(δ,ppm):160.5,158.9,153.9,153.1,150.0,144.5,141.1,134.5,131.4,127.7,127.1,125.7,123.4,11...

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Abstract

The invention relates to a pyran[2,3-b] quinoline derivative as well as a synthesis process and application thereof in tumor prevention. According to the synthesis process, multiple components are adopted to react, namely, a compound of chemical formula II, malononitrile and 4-hydroxycoumarin as raw materials, are subjected to three-component reactions in the presence of a solvent under catalysisof a solvent and the microwave radiation, then a target compound is synthesized at one step, that is, the pyran[2,3-b] quinoline derivative (formula I). The pyran[2,3-b] quinoline derivative has the advantages that multi-component reactions are carried out in the synthesis process, the pyran[2,3-b] quinoline derivative is synthesized from the three raw materials by using a 'one pot boiling' method, the derivative is a quite stable compound, and the compound has a relatively good in-vitro propagation inhibition function on a human liver tumor cell system HepG2.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to pyrano[2,3-b]quinoline derivatives, their synthesis process and their anti-tumor application. Background technique [0002] Pyran is an important class of heterocyclic compounds, and its derivatives have a wide range of biological and pharmacological activities, such as antiallergic effects (Witte, E.C.; Neubert, P.; Roesoh, A.DE 3427985, 1986), hypoglycemic effects (Jiang Hong, Wang Lijun, Zhao Zhixue, Journal of Beihua University (Natural Science Edition), 2001, 2, 489), anticancer activity (Hyama, T.; Saimoto, H.JP62181271, 1987), can be used to treat allergic tracheitis ( Chand, N.; Diamantis, W.; Sofia, R.D.Br.J.Pharmacol., 1986, 87, 443), anti-dysplasia (Brooks, G.T.; Ottridge, A.P.; Maee, D.W.Pestic. SCi., 1988, 22, 41 ) and treatment of diabetes (Suarez, M.; Ochoa, E.; Verdecia, Y.; Martin, M.; Quinteiro, C.; Seoane, J.; Soto, J.L.; Novoa, N.; Blato...

Claims

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Application Information

Patent Timeline

29 Jun 2018

Publication

CN108218883A

IPC: C07D491/153; A61P35/00

CPC: C07D491/153

Inventors: 吴玉祥; 严宾