21908-08-7

Basic information

• Product Name: Ethyl 2-forMylisonicotinate
• Synonyms: Ethyl 2-forMylisonicotinate;2-forMyl-pyridine-4-carboxylic acid 4-ethyl ester
• CAS NO: 21908-08-7
• Molecular Formula: C₉H₉NO₃
• Molecular Weight: 179.17266
• Mol File: 21908-08-7.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 288.3±25.0 °C(Predicted)
• Appearance: /
• Density: 1.204±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 1.20±0.10(Predicted)
• CAS DataBase Reference: Ethyl 2-forMylisonicotinate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 2-forMylisonicotinate(21908-08-7)
• EPA Substance Registry System: Ethyl 2-forMylisonicotinate(21908-08-7)

Safety Data

• Hazardous Substances Data: 21908-08-7(Hazardous Substances Data)

Usage

Uses

Ethyl 2-Formylisonicotinate is an intermediate used to synthesize aminoisoindoles as BACE1 inhibitors exhibiting in vivo brain reduction of β-amyloid peptides. It is also used to prepare arylmethylamino analogs of edotecarin as topoisomerase I inhibitors with antitumor activities.

Synthetic route

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → ethyl 2-formylpyridine-4-carboxylate (21908-08-7)

Conditions	Yield
Stage #1: diethyl pyridine-2,4-dicarboxylate With diisobutylaluminium hydride In tetrahydrofuran at -78℃; for 3h; Stage #2: With acetic acid In tetrahydrofuran; water at 20℃; for 1.5h;	81%
With diisobutylaluminium hydride In tetrahydrofuran; ethyl acetate; toluene at -40℃; Temperature; Solvent; Large scale; regioselective reaction;	67%
With diisobutylaluminium hydride In tetrahydrofuran; toluene at -78℃; for 3.16667h; Inert atmosphere; regioselective reaction;	39%
With lithium aluminium tetrahydride In tetrahydrofuran at -60℃; for 1.33333h;
Stage #1: diethyl pyridine-2,4-dicarboxylate With diisobutylaluminium hydride In tetrahydrofuran at -78 - 78℃; for 3h; Stage #2: In tetrahydrofuran; water at 20℃; for 1h; Cooling with ethanol-dry ice;	1.6 g

pyridine-2,4-dicarboxylic acid (499-80-9) → ethyl 2-formylpyridine-4-carboxylate (21908-08-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / 16 h / 80 °C 2: diisobutylaluminium hydride / tetrahydrofuran; toluene / 3.17 h / -78 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / Reflux 2.1: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -78 °C 2.2: 1.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / ethanol / 14 h / 70 °C 2.1: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -78 - 78 °C 2.2: 1 h / 20 °C / Cooling with ethanol-dry ice View Scheme
Multi-step reaction with 2 steps 1: thionyl chloride / Reflux 2: diisobutylaluminium hydride / ethyl acetate; tetrahydrofuran; toluene / -40 °C / Large scale View Scheme

diethyl pyridine-2,4-dicarboxylate hydrochloride → pyridine-2,4-dicarbaldehyde (6220-65-1) + ethyl 2-(hydroxymethyl)pyridine-4-carboxylate + 4-(hydroxymethyl)pyridine-2-carbaldehyde (212914-74-4) + ethyl 2-formylpyridine-4-carboxylate (21908-08-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran / -10 - 22 °C / Large scale 2: diisobutylaluminium hydride / ethyl acetate; tetrahydrofuran / 0.01 h / -20 °C / Large scale View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → pyridine-2,4-dicarbaldehyde (6220-65-1) + ethyl 2-(hydroxymethyl)pyridine-4-carboxylate + 4-(hydroxymethyl)pyridine-2-carbaldehyde (212914-74-4) + ethyl 2-formylpyridine-4-carboxylate (21908-08-7)

Conditions	Yield
With diisobutylaluminium hydride In tetrahydrofuran; ethyl acetate at -20℃; for 0.0111111h; Temperature; Time; Large scale; regioselective reaction;

pyridine-2,4-dicarboxylic acid (499-80-9) → pyridine-2,4-dicarbaldehyde (6220-65-1) + ethyl 2-(hydroxymethyl)pyridine-4-carboxylate + 4-(hydroxymethyl)pyridine-2-carbaldehyde (212914-74-4) + ethyl 2-formylpyridine-4-carboxylate (21908-08-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / Reflux 2: diisobutylaluminium hydride / ethyl acetate; tetrahydrofuran / 0.01 h / -20 °C / Large scale View Scheme

furan-2-ylmethanamine (617-89-0) + ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → 2-{[(furan-2-ylmethyl)amino]methyl}isonicotinic acid ethyl ester

Conditions	Yield
Stage #1: furan-2-ylmethanamine; ethyl 2-formylpyridine-4-carboxylate With acetic acid In dichloromethane at 20℃; for 0.5h; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 20℃;	99%

(R)-7′-bis-(3,5-di-tert-butylphenyl)phosphino-7′-amino-1,1′-spiroindene (1219025-18-9) + ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → C54H67N2O2P

Conditions	Yield
With acetic acid In methanol at 20℃; for 2h; Inert atmosphere; Schlenk technique;	96%

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) + benzylamine (100-46-9) → ethyl 2-[(benzylamino)methyl]isonicotinate

Conditions	Yield
Stage #1: ethyl 2-formylpyridine-4-carboxylate; benzylamine With acetic acid In dichloromethane at 20℃; for 0.25h; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 16h;	93%

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) + 2-methoxyethylamine (109-85-3) → (E)-ethyl-2-((2-methoxyethylimino)methyl)isonicotinate

Conditions	Yield
In toluene	92%

diphenyl hydrogen phosphite (4712-55-4) + ethyl 2-formylpyridine-4-carboxylate (21908-08-7) + aniline (62-53-3) → ethyl 2-[anilino(diphenoxyphosphoryl)methyl]pyridine-4-carboxylate

Conditions	Yield
In isopropyl alcohol at 20℃; for 2.5h;	83%

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) + (bis-(2-methoxyethyl)amino)sulfur trufluoride (202289-38-1) → 2-difluoromethylisonicotinic acid ethyl ester (1192539-75-5)

Conditions	Yield
In dichloromethane at 0 - 20℃; for 5h;	73.8%

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → 2-(hydroxyimino-methyl)-isonicotinic acid ethyl ester (10177-26-1)

Conditions	Yield
With hydroxylamine hydrochloride; sodium hydrogencarbonate In water Yield given;

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → 4-Carboxy-2-(hydroxyimino-methyl)-1-methyl-pyridinium; iodide

Conditions	Yield
Multi-step reaction with 3 steps 1: NH2OH*HCl, NaHCO3 / H2O 2: 70 percent / dimethylformamide / 12 h / 60 °C 3: NaOH, H2O View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → 4-Ethoxycarbonyl-2-(hydroxyimino-methyl)-1-methyl-pyridinium; iodide

Conditions	Yield
Multi-step reaction with 2 steps 1: NH2OH*HCl, NaHCO3 / H2O 2: 70 percent / dimethylformamide / 12 h / 60 °C View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) + orthoformic acid triethyl ester (122-51-0) → 2-diethoxymethyl-isonicotinic acid ethyl ester (23504-39-4)

Conditions	Yield
With hydrogenchloride; potassium carbonate In diethyl ether; ethanol

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) + trimethyl orthoformate (149-73-5) → methyl 2-(dimethoxymethyl)isonicotinate

Conditions	Yield
With pyridinium p-toluenesulfonate In methanol for 19h; Reflux;

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → C11H17N3O2*ClH (1596348-60-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 2: lithium hydroxide; water / methanol; tetrahydrofuran / 20 °C View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) + N,N-dimethylethylenediamine (108-00-9) → ethyl 2-({[2-(dimethylamino)ethyl]amino}methyl)pyridine-4-carboxylate (1596348-63-8)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃;

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → 2-(dimethoxymethyl)pyridine-4-carbaldehyde

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 2: diisobutylaluminium hydride / toluene / 1.5 h / -78 °C / Inert atmosphere View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → N-{[2-(dimethoxymethyl)pyridin-4-yl]methylidene}hydroxylamine

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 2: diisobutylaluminium hydride / toluene / 1.5 h / -78 °C / Inert atmosphere 3: sodium carbonate; hydroxylamine hydrochloride / water; ethanol / 3 h / 20 °C / Inert atmosphere View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → [2-(dimethoxymethyl)pyridin-4-yl]methanamine

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 2: diisobutylaluminium hydride / toluene / 1.5 h / -78 °C / Inert atmosphere 3: sodium carbonate; hydroxylamine hydrochloride / water; ethanol / 3 h / 20 °C / Inert atmosphere 4: hydrogen; palladium on activated charcoal / methanol / 2327.23 Torr / Inert atmosphere View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → N-{[2-(dimethoxymethyl)pyridin-4-yl]methyl}cyclopropanamine

Conditions	Yield
Multi-step reaction with 3 steps 1.1: pyridinium p-toluenesulfonate / methanol / 60 °C / Inert atmosphere 2.1: diisobutylaluminium hydride / toluene / 1.5 h / -78 °C / Inert atmosphere 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / 20 °C / Inert atmosphere 3.2: 20 °C View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) + trimethyl orthoformate (149-73-5) → ethyl 2-(dimethoxymethyl)pyridine-4-carboxylate

Conditions	Yield
With pyridinium p-toluenesulfonate In methanol at 60℃; Inert atmosphere;

N,N-dimethylglycineamide hydrochloride (118872-69-8) + ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → ethyl 2-({[(dimethylcarbamoyl)methyl]amino}methyl)pyridine-4-carboxylate

Conditions	Yield
Stage #1: N,N-dimethylglycineamide hydrochloride; ethyl 2-formylpyridine-4-carboxylate With triethylamine In 1,2-dichloro-ethane at 20℃; for 2h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 20℃;

n-propylmagnesium bromide (927-77-5) + ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → ethyl 2-(1-hydroxybutyl)pyridine-4-carboxylate

Conditions	Yield
With water In tetrahydrofuran at 0 - 20℃;

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → 2-{[(furan-2-ylmethyl)amino]methyl}pyridine-4-carboxylic acid (1596347-76-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: acetic acid / dichloromethane / 0.5 h / 20 °C 1.2: 20 °C 2.1: water; lithium hydroxide / acetonitrile / 20 °C View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → lithium 2-[(benzylamino)methyl]isonicotinate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: acetic acid / dichloromethane / 0.25 h / 20 °C 1.2: 16 h / 20 °C 2.1: water; lithium hydroxide / tetrahydrofuran / 16 h / 20 °C View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → 2-(difluoromethyl)-N-methoxy-N-methylisonicotinamide

Conditions	Yield
Multi-step reaction with 2 steps 1: dichloromethane / 5 h / 0 - 20 °C 2: isopropylmagnesium bromide / tetrahydrofuran / 1.5 h / 0 - 15 °C View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → 1-(2-(difluoromethyl)pyridin-4-yl)ethan-1-one (1256788-49-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: dichloromethane / 5 h / 0 - 20 °C 2: isopropylmagnesium bromide / tetrahydrofuran / 1.5 h / 0 - 15 °C 3: methylmagnesium bromide / tetrahydrofuran / 3 h / 0 °C View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → (R)-N-(1-(2-(difluoromethyl)pyridin-4-yl)ethylidene)-2-methylpropane-2-sulfinamide

Conditions	Yield
Multi-step reaction with 4 steps 1: dichloromethane / 5 h / 0 - 20 °C 2: isopropylmagnesium bromide / tetrahydrofuran / 1.5 h / 0 - 15 °C 3: methylmagnesium bromide / tetrahydrofuran / 3 h / 0 °C 4: titanium(IV) tetraethanolate / tetrahydrofuran / 80 °C View Scheme

ethyl 2-formylpyridine-4-carboxylate (21908-08-7) → (R)-N-(1-(2-(difluoromethyl)pyridin-4-yl)ethyl)-2-methylpropane-2-sulfinamide

Conditions	Yield
Multi-step reaction with 5 steps 1: dichloromethane / 5 h / 0 - 20 °C 2: isopropylmagnesium bromide / tetrahydrofuran / 1.5 h / 0 - 15 °C 3: methylmagnesium bromide / tetrahydrofuran / 3 h / 0 °C 4: titanium(IV) tetraethanolate / tetrahydrofuran / 80 °C 5: sodium tetrahydroborate / water; tetrahydrofuran / 4 h / -78 - 0 °C View Scheme

Upstream product

• 499-80-9 pyridine-2,4-dicarboxylic acid 
• 41438-38-4 diethyl pyridine-2,4-dicarboxylate 

Downstream Products

• 1596348-32-1 KDM5-C70 

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