58610-61-0

Basic information

• Product Name: ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate
• CAS NO: 58610-61-0
• Molecular Formula: C₁₀H₁₀N₂O₃
• Molecular Weight: 206.198
• Mol File: 58610-61-0.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 387.7°C at 760 mmHg
• Flash Point: 188.3°C
• Density: 1.26g/cm³
• Vapor Pressure: 3.23E-06mmHg at 25°C
• Refractive Index: 1.536
• CAS DataBase Reference: ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate(58610-61-0)
• EPA Substance Registry System: ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate(58610-61-0)

Safety Data

• Hazardous Substances Data: 58610-61-0(Hazardous Substances Data)

Usage

General Description

Ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate is a chemical compound with the molecular formula C11H12N2O3. It is commonly used as a building block in the synthesis of pharmaceuticals and agrochemicals, and it also exhibits potential biological activity. ethyl 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-carboxylate belongs to the class of dihydropyridine derivatives, which are known for their diverse pharmacological properties, including calcium channel blocking and antioxidant activities. Additionally, it has been identified as a potential anti-inflammatory and antitumor agent, making it of interest in medicinal chemistry research. 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.

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

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

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