58610-61-0

Usage

Uses

Used in Pharmaceutical Industry:
Ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate is used as a building block for the synthesis of various pharmaceuticals due to its diverse pharmacological properties. Its calcium channel blocking and antioxidant activities contribute to the development of drugs for treating cardiovascular diseases and other conditions.
Used in Agrochemical Industry:
In the agrochemical industry, ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate is utilized as a key intermediate in the synthesis of agrochemicals, such as pesticides and herbicides, to enhance crop protection and yield.
Used in Medicinal Chemistry Research:
Ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate is used as a potential anti-inflammatory and antitumor agent in medicinal chemistry research. Its biological activity and diverse pharmacological properties make it a promising candidate for the development of new therapeutic agents to treat inflammation and cancer.
Overall, ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate is a versatile chemical with various applications in the fields of medicine and agriculture, playing a crucial role in the synthesis of pharmaceuticals, agrochemicals, and as a subject of research for new therapeutic agents.

Synthetic route

ethyl (3E)-4-ethoxy-2-oxopent-3-enoate + cyanoacetic acid amide (107-91-5) → ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0)

Conditions	Yield
With potassium carbonate In acetone Heating;	82%
With potassium carbonate In acetone Reflux;	60%

ethyl 4-ethoxy-2-oxopent-3-enoate + cyanoacetic acid amide (107-91-5) → ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0)

Conditions	Yield
With potassium carbonate In acetone for 10h; Reflux;	65.7%
With potassium carbonate In acetone for 10h; Inert atmosphere; Reflux;	65.7%

ethyl 2,4-diketopentanoate (615-79-2) → ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonium chloride / ethanol / 20 °C 2: potassium carbonate / acetone / 10 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: ammonium chloride / ethanol / 20 °C / Inert atmosphere 2: potassium carbonate / acetone / 10 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 2 steps 1: ammonium chloride / ethanol / 12 h / 20 °C 2: potassium carbonate / acetone / Reflux View Scheme

4-bromoethylbutanoate (2969-81-5) + ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 5-Cyano-1-(3-ethoxycarbonyl-propyl)-4-methyl-6-oxo-1,6-dihydro-pyridine-2-carboxylic acid ethyl ester (154597-41-8) + 5-Cyano-6-(3-ethoxycarbonyl-propoxy)-4-methyl-pyridine-2-carboxylic acid ethyl ester

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 3.5h;	A 20% B 70%

propargyl bromide (106-96-7) + ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 5-Cyano-4-methyl-6-oxo-1-prop-2-ynyl-1,6-dihydro-pyridine-2-carboxylic acid ethyl ester (181512-47-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide	65%

trimethoxonium tetrafluoroborate (420-37-1) + ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → ethyl 5-cyano-6-methoxy-4-methylpyridine-2-carboxylate

Conditions	Yield
Stage #1: trimethoxonium tetrafluoroborate; ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate In dichloromethane at 20℃; for 24h; Stage #2: With sodium hydroxide In dichloromethane for 0.166667h;	52.9%

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → ethyl 5-cyano-6-methoxy-4-methylpyridine-2-carboxylate

Conditions	Yield
With trimethoxonium tetrafluoroborate In dichloromethane at 20℃; for 24h; Inert atmosphere;	52.9%

di-tert-butyl dicarbonate (24424-99-5) + ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → ethyl 5-((bis(tert-butoxycarbonyl)amino)methyl)-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate

Conditions	Yield
With hydrogen In methanol at 20℃; for 16h;	33%

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) + (MeO)3BF4 → ethyl 5-cyano-6-methoxy-4-methylpyridine-2-carboxylate

Conditions	Yield
In dichloromethane at 20℃; for 48h;	32%

acrylic acid methyl ester (292638-85-8) + ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 2-(methoxycarbonyl)-6-cyano-7-methyl-1,5-dioxo-Δ6(8)-tetrahydroindolizine

Conditions	Yield
With potassium carbonate 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h; Yield given. Multistep reaction;

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 7-methyl-9-oxo-9,11-dihydroindolizino[1,2-b]quinoline-8-carbonitrile (66917-21-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 65 percent / K2CO3 / dimethylformamide 2: 95 percent / NaOH / dimethylformamide; H2O 3: CDI / tetrahydrofuran 4: 75 percent / Ac2O / Heating View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 5-Cyano-4-methyl-6-oxo-1-prop-2-ynyl-1,6-dihydro-pyridine-2-carboxylic acid (181512-51-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / K2CO3 / dimethylformamide 2: 95 percent / NaOH / dimethylformamide; H2O View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 2-methoxy-7-methyl-9-oxo-9,11-dihydroindolizino[1,2-b]quinoline-8-carbonitrile

Conditions	Yield
Multi-step reaction with 5 steps 1: 65 percent / K2CO3 / dimethylformamide 2: 95 percent / NaOH / dimethylformamide; H2O 3: 83 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (HOBT) / CH2Cl2 4: CH2Cl2 / 20 °C 5: acetonitrile / 6 h / Heating View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 5-Cyano-4-methyl-6-oxo-1-prop-2-ynyl-1,6-dihydro-pyridine-2-carboxylic acid (4-methoxy-phenyl)-amide (181512-25-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 65 percent / K2CO3 / dimethylformamide 2: 95 percent / NaOH / dimethylformamide; H2O 3: 83 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (HOBT) / CH2Cl2 View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 5-Cyano-N-(4-methoxy-phenyl)-4-methyl-6-oxo-1-prop-2-ynyl-1,6-dihydro-pyridine-2-carboximidic acid methyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1: 65 percent / K2CO3 / dimethylformamide 2: 95 percent / NaOH / dimethylformamide; H2O 3: 83 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (HOBT) / CH2Cl2 4: CH2Cl2 / 20 °C View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 2-[(5-Cyano-4-methyl-6-oxo-1-prop-2-ynyl-1,6-dihydro-pyridine-2-carbonyl)-amino]-benzoic acid (181512-33-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 65 percent / K2CO3 / dimethylformamide 2: 95 percent / NaOH / dimethylformamide; H2O 3: CDI / tetrahydrofuran View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → ethyl 2-(6′-cyan-5′-oxo-3′,5′-dihydro-2′H-spiro[[1,3]dioxolane-2,1′-indolizine]-7′-yl)acetate (58610-65-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 6'-cyano-α-ethyl-2',3'-dihydro-5'-oxospiro<1,3-dioxolane-2,1'(5'H)-indolizine>-7'-acetic acid, ethyl ester (58610-66-5)

Conditions

Yield

Multi-step reaction with 5 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DME, -78 deg C, 5 min, 2.) DME, a.) -78 deg C, 1.5 h, b.) RT, overnight View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 1,5-dioxo(5'-ethyl-2'H,5'H,6'H-6-oxopyrano)<3',4'-f>-Δ6(8)-tetrahydroindolizine (73428-00-9)

Conditions

Yield

Multi-step reaction with 9 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DME, -78 deg C, 5 min, 2.) DME, a.) -78 deg C, 1.5 h, b.) RT, overnight 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating 9: 88 percent / H2SO4 / 1,2-dimethoxy-ethane / 24 h / 50 °C View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 6-cyano-7-methyl-1,5-dioxo-Δ6(8)-tetrahydroindolizine (58610-63-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → (+/-)-10-methoxycamptothecin (64439-80-1)

Conditions

Yield

Multi-step reaction with 11 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DME, -78 deg C, 5 min, 2.) DME, a.) -78 deg C, 1.5 h, b.) RT, overnight 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating 9: 88 percent / H2SO4 / 1,2-dimethoxy-ethane / 24 h / 50 °C 10: 2.) p-toluenesulfonic acid / 1.) toluene, reflux, 30 min, 2.) toluene, reflux, 2.5 h 11: 61 percent / oxygen, cupric chloride, dimethylamine / dimethylformamide; H2O / 20 h View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 4-ethyl-1,12-dihydro-14-H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-(4H)-dione (34141-35-0)

Conditions

Yield

Multi-step reaction with 10 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DME, -78 deg C, 5 min, 2.) DME, a.) -78 deg C, 1.5 h, b.) RT, overnight 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating 9: 88 percent / H2SO4 / 1,2-dimethoxy-ethane / 24 h / 50 °C 10: 2.) p-toluenesulfonic acid / 1.) toluene, ref;ux, 30 min, 2.) toluene, reflux, 3 h View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → dl-10-hydroxycamptothecin

Conditions

Yield

Multi-step reaction with 12 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DME, -78 deg C, 5 min, 2.) DME, a.) -78 deg C, 1.5 h, b.) RT, overnight 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating 9: 88 percent / H2SO4 / 1,2-dimethoxy-ethane / 24 h / 50 °C 10: 2.) p-toluenesulfonic acid / 1.) toluene, reflux, 30 min, 2.) toluene, reflux, 2.5 h 11: 61 percent / oxygen, cupric chloride, dimethylamine / dimethylformamide; H2O / 20 h 12: 48 percent / HBr / 1.5 h / Heating View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 6-(acetoxymethyl)-1,1'-(ethylenedioxy)-7-<1'-(ethoxycarbonyl)propyl>-5-oxo-Δ6(8)-tetrahydroindolizine (73427-97-1)

Conditions

Yield

Multi-step reaction with 8 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DME, -78 deg C, 5 min, 2.) DME, a.) -78 deg C, 1.5 h, b.) RT, overnight 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → camptothecin (31456-25-4)

Conditions

Yield

Multi-step reaction with 11 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DME, -78 deg C, 5 min, 2.) DME, a.) -78 deg C, 1.5 h, b.) RT, overnight 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating 9: 88 percent / H2SO4 / 1,2-dimethoxy-ethane / 24 h / 50 °C 10: 2.) p-toluenesulfonic acid / 1.) toluene, ref;ux, 30 min, 2.) toluene, reflux, 3 h 11: 41 percent / O2, cupric chloride, dimethylamine / dimethylformamide; H2O View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 4-Hydroxy-4-(2-methoxy-ethyl)-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione (73427-84-6)

Conditions

Yield

Multi-step reaction with 11 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DMF, 10 min, 2.) DMF, 50 deg C, 24 h 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating 9: 76 percent / H2SO4 / 1,2-dimethoxy-ethane / 24 h / 50 °C 10: 2.) p-toluenesulfonic acid / 1.) toluene, reflux, 30 min, 2.) toluene, reflux, 3 h 11: 50 percent / oxygen, cupric nitrate trihydrate, dimethylamine / dimethylformamide; H2O / 1 h View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → dl-azacamptothecin (73466-16-7)

Conditions

Yield

Multi-step reaction with 11 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DME, -78 deg C, 5 min, 2.) DME, a.) -78 deg C, 1.5 h, b.) RT, overnight 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating 9: 88 percent / H2SO4 / 1,2-dimethoxy-ethane / 24 h / 50 °C 10: 52 percent / 2 h / 100 °C 11: 24 percent / cupric nitrate trihydrate, dimethylamine, oxygen / dimethylformamide; H2O / 1 h View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 7’-methyl-5’-oxo-3’,5’-dihydro-2’H-spiro[[1,3]dioxolane-2,1‘-indolizine]-6’-carbonitrile (58610-64-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 1,5-dioxo<5'-(methoxyethyl)-2'H,5'H,6'H-6-oxopyrano><3',4',-f>-Δ6(8)-tetrahydroindolizine (73428-01-0)

Conditions

Yield

Multi-step reaction with 9 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DMF, 10 min, 2.) DMF, 50 deg C, 24 h 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating 9: 76 percent / H2SO4 / 1,2-dimethoxy-ethane / 24 h / 50 °C View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → 2-(methoxycarbonyl)-3-<2'-(methoxycarbonyl)ethyl>-6-cyano-7-methyl-1,5-dioxo-Δ6(8)-tetrahydroindolizine

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 78 percent / K2CO3 / dimethylformamide / 10 h / Heating View Scheme

ethyl 5-cyano-4-methyl-6-oxo-1, 6-dihydropyridine-2-carboxylate (58610-61-0) → dl-12-aza-20-deoxycamptothecin (73427-81-3)

Conditions

Yield

Multi-step reaction with 10 steps 1: 1.) K2CO3 / 1.) DMF, 45 deg C, 2.) DMF, 45 deg C, 40 h 2: 89 percent / conc. HCl / acetic acid / 2 h / Heating 3: 93 percent / p-toluenesulfonic acid / toluene / 20 h / Heating 4: 1.) KH, ethanol, 2.) diethyl carbonate / 1.) toluene, reflux, 10 min, 2.) toluene, reflux, 3 h 5: 1.) potassium tert-butoxide / 1.) DME, -78 deg C, 5 min, 2.) DME, a.) -78 deg C, 1.5 h, b.) RT, overnight 6: 100 percent / H2 / Raney nickel / acetic acid / 6 h / 45 °C / 2585.7 Torr 7: NaNO2 / acetic anhydride; acetic acid / 2 h / 0 °C 8: CCl4 / Heating 9: 88 percent / H2SO4 / 1,2-dimethoxy-ethane / 24 h / 50 °C 10: 52 percent / 2 h / 100 °C View Scheme

Upstream product

• 107-91-5 cyanoacetic acid amide 
• 615-79-2 ethyl 2,4-diketopentanoate 

Downstream Products

• 1346575-74-3 tert-butyl ((5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate 
• 58610-64-3 7’-methyl-5’-oxo-3’,5’-dihydro-2’H-spiro[[1,3]dioxolane-2,1‘-indolizine]-6’-carbonitrile 
• 31456-25-4 camptothecin 
• 64439-81-2 dl-10-hydroxycamptothecin 
• 58610-63-2 6-cyano-7-methyl-1,5-dioxo-Δ⁶⁽⁸⁾-tetrahydroindolizine 
• 181512-33-4 2-[(5-Cyano-4-methyl-6-oxo-1-prop-2-ynyl-1,6-dihydro-pyridine-2-carbonyl)-amino]-benzoic acid 
• 181512-25-4 5-Cyano-4-methyl-6-oxo-1-prop-2-ynyl-1,6-dihydro-pyridine-2-carboxylic acid (4-methoxy-phenyl)-amide 

Relevant academic research and scientific papers

PYRAZOLOPYRIDINE PYRAZOLOPYRIMIDINE AND RELATED COMPOUNDS

In one aspect this invention relates generally to compounds of Formula: and sub-formulas thereof, or a tautomer of each thereof, a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing, where X1, L1, L3, and R3 are described herein.

METHOD OF TREATMENT

The present invention relates to a method of treating T cell mediated inflammatory immune diseases or T cell mediated hypersensitivity diseases, which comprises administering to a human in need thereof an effective amount of a compound which inhibits EZH2 and/or EZH1, or a pharmaceutically acceptable salt thereof.

ENHANCER OF ZESTE HOMOLOG 2 INHIBITORS

This invention relates to novel substituted benzamide according to Formula (I) which are inhibitors of Enhancer of Zeste Homolog 2 (EZH2), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the treatment of cancers.

Novel syntheses of camptothecin alkaloids. Part I. Intramolecular [4 + 2] cycloadditions of N-arylimidates and 4H-3,1-benzoxazin-4-ones as 2-aza-1,3-dienes

The first reported intramolecular [4 + 2] cycloadditions of both N-arylimidates and 4H-3,1-benzoxazin-4-ones acting as 2-aza-1,3-dienes are described. Reaction with unactivated alkynes leads to pyrrolo[3,4-b]quinolines which constitute the ABC ring system of camptothecins.