Synthetic method of coumarin-pyrrole compound

Abstract

The invention discloses a synthesis method of coumarin-pyrrole compounds. In a reaction solvent, 4-aminocoumarin compounds and disubstituted acetylene compounds are used as raw materials, under the catalysis of palladium (II) and the action of oxidants, The reaction yields coumarin-pyrrole compounds. The invention has cheap and easy-to-obtain raw materials, mild reaction conditions, simple and convenient synthetic route, high atom economy and good industrial application prospect.

Description

technical field

[0001] The invention belongs to the technical field of organic compound technology application, and specifically relates to a synthesis method of coumarin-pyrrole compounds. Background technique

[0002] Since nitrogen heterocycles are ubiquitous in natural products and medicines, they are the key areas of research. As we all know, pyrrole is a five-membered nitrogen-containing heterocyclic compound, and many drug molecules contain such a skeleton, so it is used as a basic building block in medicinal chemistry, such as formula A, a hypolipidemic drug marketed by Pfizer under the trade name Lipitor Atorvastatin (Atorvastatin) 1, lamellarin D (Lamellarin D), which is cytotoxic to many different cancer cells and has a strong inhibitory effect on human topoisomerase I60 2, non-steroidal antipyretic Anti-inflammatory drug (NSAID) Zomepirac (Zomepirac)3 and potential anticancer drug4.

[0003]

[0004] Formula A. Several drug molecules containing pyrrole struc...

Examples

Embodiment 1

[0026]

[0027] coumarins 1a (0.2mmol), disubstituted acetylene compounds 2a (0.6mmol), palladium acetate (0.02mmol) and copper acetate (0.04mmol) were added in DMSO (2mL). The reaction mixture was stirred at normal temperature and pressure under an oxygen atmosphere for 72 hours. After the completion of the reaction monitored by TLC, the organic solvent was removed by distillation under reduced pressure to obtain the crude product, and the product was obtained by flash column chromatography (ethyl acetate:n-hexane=1:4) 3aa (90%). 1 HNMR (500MHz, d 6 -DMSO,298K):δ12.80(s,1H),8.37–8.17(m,1H),7.56–7.20(m,13H). 13 CNMR (125MHz, d 6 -DMSO,298K):δ157.74,151.61,135.78,133.88,133.55,131.49,131.07,129.24,128.82,128.18,128.09,127.14,124.39,122.11,121.09,117.00,113.86,107.29,40.73,40.46,40.18,39.90, 39.62, 39.35, 39.07.HRMS(ESI): calculated value [C 23 h 15 NO 2 +H] + 338.1176, actual value 338.1177.

Embodiment 2

[0029]

[0030] The operation steps are the same as in Example 1, and the productive rate is 89%. 1 HNMR (500MHz, d 6 -DMSO,298K):δ12.72(s,1H),8.11(s,1H),7.65–7.08(m,12H),2.43(s,3H). 13 CNMR (125MHz, d 6 -DMSO,298K):δ157.87,149.80,135.82,133.73,133.61,133.49,131.48,131.06,130.09,128.80,128.70,128.13,128.10,127.14,121.91,121.06,116.77,113.52,107.32,40.73,40.46,40.18, 39.90, 39.62, 39.35, 39.07, 20.99.HRMS(ESI): calculated value [C 24 h 17 NO 2 -H] - 350.1187, the actual value is 350.1197.

Embodiment 3

[0032]

[0033] The operation steps are the same as in Example 1, and the productive rate is 99%. 1 HNMR (500MHz, d 6 -DMSO,298K):δ12.75(s,1H),8.16(s,1H),7.65–6.92(m,12H),2.74(q, J =7.6Hz,2H),1.30(t, J =7.6Hz,3H). 13 CNMR (125MHz, d 6-DMSO,298K):δ158.01,150.04,139.93,136.07,133.85,133.70,131.62,131.17,129.18,128.93,128.85,128.27,128.22,127.25,121.15,120.79,116.91,113.68,107.36,40.73,40.46,40.18, 39.90, 39.62, 39.35, 39.07, 28.18, 15.89. HRMS (ESI): calculated value [C 25 h 19 NO 2 -H] - 364.1343, actual value 364.1346.

technical field

[0001] The invention belongs to the technical field of organic compound technology application, and specifically relates to a synthesis method of coumarin-pyrrole compounds. Background technique

[0002] Since nitrogen heterocycles are ubiquitous in natural products and medicines, they are the key areas of research. As we all know, pyrrole is a five-membered nitrogen-containing heterocyclic compound, and many drug molecules contain such a skeleton, so it is used as a basic building block in medicinal chemistry, such as formula A, a hypolipidemic drug marketed by Pfizer under the trade name Lipitor Atorvastatin (Atorvastatin) 1, lamellarin D (Lamellarin D), which is cytotoxic to many different cancer cells and has a strong inhibitory effect on human topoisomerase I60 2, non-steroidal antipyretic Anti-inflammatory drug (NSAID) Zomepirac (Zomepirac)3 and potential anticancer drug4.

[0003]

[0004] Formula A. Several drug molecules containing pyrrole struc...

Examples

Embodiment 1

[0026]

[0027] coumarins 1a (0.2mmol), disubstituted acetylene compounds 2a (0.6mmol), palladium acetate (0.02mmol) and copper acetate (0.04mmol) were added in DMSO (2mL). The reaction mixture was stirred at normal temperature and pressure under an oxygen atmosphere for 72 hours. After the completion of the reaction monitored by TLC, the organic solvent was removed by distillation under reduced pressure to obtain the crude product, and the product was obtained by flash column chromatography (ethyl acetate:n-hexane=1:4) 3aa (90%). 1 HNMR (500MHz, d 6 -DMSO,298K):δ12.80(s,1H),8.37–8.17(m,1H),7.56–7.20(m,13H). 13 CNMR (125MHz, d 6 -DMSO,298K):δ157.74,151.61,135.78,133.88,133.55,131.49,131.07,129.24,128.82,128.18,128.09,127.14,124.39,122.11,121.09,117.00,113.86,107.29,40.73,40.46,40.18,39.90, 39.62, 39.35, 39.07.HRMS(ESI): calculated value [C 23 h 15 NO 2 +H] + 338.1176, actual value 338.1177.

Embodiment 2

[0029]

[0030] The operation steps are the same as in Example 1, and the productive rate is 89%. 1 HNMR (500MHz, d 6 -DMSO,298K):δ12.72(s,1H),8.11(s,1H),7.65–7.08(m,12H),2.43(s,3H). 13 CNMR (125MHz, d 6 -DMSO,298K):δ157.87,149.80,135.82,133.73,133.61,133.49,131.48,131.06,130.09,128.80,128.70,128.13,128.10,127.14,121.91,121.06,116.77,113.52,107.32,40.73,40.46,40.18, 39.90, 39.62, 39.35, 39.07, 20.99.HRMS(ESI): calculated value [C 24 h 17 NO 2 -H] - 350.1187, the actual value is 350.1197.

Embodiment 3

[0032]

[0033] The operation steps are the same as in Example 1, and the productive rate is 99%. 1 HNMR (500MHz, d 6 -DMSO,298K):δ12.75(s,1H),8.16(s,1H),7.65–6.92(m,12H),2.74(q, J =7.6Hz,2H),1.30(t, J =7.6Hz,3H). 13 CNMR (125MHz, d 6-DMSO,298K):δ158.01,150.04,139.93,136.07,133.85,133.70,131.62,131.17,129.18,128.93,128.85,128.27,128.22,127.25,121.15,120.79,116.91,113.68,107.36,40.73,40.46,40.18, 39.90, 39.62, 39.35, 39.07, 28.18, 15.89. HRMS (ESI): calculated value [C 25 h 19 NO 2 -H] - 364.1343, actual value 364.1346.

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