41438-38-4

Basic information

• Product Name: 2,4-DIETHYLPYRIDINE DICARBOXYLATE
• Synonyms: DIETHYL 2,4-PYRIDINECARBOXYLATE;2,4-PYRIDINEDICARBOXYLIC ACID DIETHYL ESTER;2,4-DPD;2,4-DIETHYLPYRIDINE DICARBOXYLATE;2,4-Pyridinedicarboxylic;2,4-pyridinedicarboxylicacid,ethylester;diethyl 2,4-pyridinedicarboxylic acid;2,4-Pdc diethyl ester
• CAS NO: 41438-38-4
• Molecular Formula: C₁₁H₁₃NO₄
• Molecular Weight: 223.23
• Product Categories: Pyridines, Pyrimidines, Purines and Pteredines
• Mol File: 41438-38-4.mol
• Article Data: 13

Chemical Properties

• Melting Point: 31 °C
• Boiling Point: 330.9 °C at 760 mmHg
• Flash Point: 153.9 °C
• Appearance: /
• Density: 1.166 g/cm³
• Vapor Pressure: 0.000162mmHg at 25°C
• Refractive Index: 1.508
• Storage Temp.: 2-8°C
• Solubility: ≤50mg/ml in ethanol;20mg/ml in DMSO;30mg/ml in dimethyl formamide
• PKA: -0.69±0.10(Predicted)
• CAS DataBase Reference: 2,4-DIETHYLPYRIDINE DICARBOXYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: 2,4-DIETHYLPYRIDINE DICARBOXYLATE(41438-38-4)
• EPA Substance Registry System: 2,4-DIETHYLPYRIDINE DICARBOXYLATE(41438-38-4)

Safety Data

• Hazardous Substances Data: 41438-38-4(Hazardous Substances Data)

Usage

Biological Activity

2,4-dpd is a cell permeable, competitive inhibitor of the oxygen-sensing enzyme hif-α prolyl hydroxylase (hif-ph) [1].hypoxia-inducible factor (hif) is a transcription factor with a key role in cellular responses to hypoxia in a variety of organisms. the hif system plays an important role in angiogenesis, erythropoiesis, energy utilization, glucose/energy metabolism, tumour development, and ischaemic/hypoxic disease. genetic or pharmacological inactivation of the hif hydroxylases results in a constitutive activation of the hif pathway with little or even absent regulation by oxygen remaining. the oxygen-sensing enzyme hif-α prolyl hydroxylase catalyzes hydroxylation of specific prolyl and asparaginyl residues in the regulatory hif-α subunits [2].exposure to 2,4-dpd limited prolyl 4-hydroxylase activity in c. elegans., where their esters are hydrolyzed to form competitors of a -ketoglutarate. 2,4-dpd showed dramatic effects among the progeny. when exposed to a high level of 2,4-dpd (2.7 mm), all progeny died regardless of genotype of c. elegans. the dead embryos arrested at the twofold stage [1].

references

[1] friedman l, higgin j j, moulder g, et al. prolyl 4-hydroxylase is required for viability and morphogenesis in caenorhabditis elegans[j]. proceedings of the national academy of sciences, 2000, 97(9): 4736-4741.[2] schofield c j, ratcliffe p j. signalling hypoxia by hif hydroxylases[j]. biochemical and biophysical research communications, 2005, 338(1): 617-626.

InChI:InChI=1/C11H13NO4/c1-3-15-10(13)8-5-6-12-9(7-8)11(14)16-4-2/h5-7H,3-4H2,1-2H3

Synthetic route

pyridine-2,4-dicarboxylic acid (499-80-9) + ethanol (64-17-5) → diethyl pyridine-2,4-dicarboxylate (41438-38-4)

Conditions	Yield
With toluene-4-sulfonic acid for 24h; Heating;	100%
With toluene-4-sulfonic acid In toluene at 110℃;	88%
Stage #1: ethanol With thionyl chloride at 0℃; for 0.5h; Inert atmosphere; Stage #2: pyridine-2,4-dicarboxylic acid In ethanol for 3h; Inert atmosphere; Reflux;	82%

pyridine (110-86-1) + 2-oxo-propionic acid ethyl ester (617-35-6) → ethyl-2-picolinate (2524-52-9) + isonicotinic acid ethylester (1570-45-2) + diethyl pyridine-2,4-dicarboxylate (41438-38-4)

Conditions	Yield
With sulfuric acid; dihydrogen peroxide; iron(II) sulfate In dichloromethane; water at -10 - 0℃; for 0.25h; Product distribution; Variation of mole ratio of the base and the peroxide.;	A 28 % Chromat. B 4 % Chromat. C 37 % Chromat.

pyridine-2,4-dicarboxylic acid (499-80-9) → diethyl pyridine-2,4-dicarboxylate (41438-38-4)

Conditions	Yield
With sulfuric acid In ethanol at 70℃; for 14h;	6 g

diethyl pyridine-2,4-dicarboxylate hydrochloride + triethylamine (121-44-8) → diethyl pyridine-2,4-dicarboxylate (41438-38-4) + triethylamine hydrochloride (554-68-7)

Conditions	Yield
In tetrahydrofuran at -10 - 22℃; Large scale;

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → ethyl 2-(hydroxymethyl)pyridine-4-carboxylate

Conditions	Yield
Stage #1: diethyl pyridine-2,4-dicarboxylate With sodium tetrahydroborate In ethanol at 5℃; Stage #2: With calcium chloride In ethanol	91%
With sodium tetrahydroborate; calcium chloride In ethanol at -10 - -5℃; for 2.5h;	69%
With sodium tetrahydroborate; calcium chloride at -15 - 0℃;
With sodium tetrahydroborate; calcium chloride In ethanol at 0℃;

diethyl pyridine-2,4-dicarboxylate (41438-38-4) + Cyclopropylamine (765-30-0) → ethyl 2-(cyclopropylcarbamoyl)pyridine-4-carboxylate (1353657-39-2)

Conditions	Yield
With magnesium chloride In ethanol at 0 - 20℃; for 48h;	91%

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2,4-diacetylpyridine (20857-17-4)

Conditions	Yield
Stage #1: diethyl pyridine-2,4-dicarboxylate With sodium ethanolate In ethyl acetate at 70 - 80℃; for 2h; Stage #2: With hydrogenchloride In ethyl acetate for 4h; Heating;	88%

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2,4-Bis(hydroxymethyl)pyridin (21071-04-5)

Conditions	Yield
With sodium tetrahydroborate In ethanol at 20℃; for 72h;	82%

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

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2,4-lutidine (108-47-4)

Conditions	Yield
With sulfuric acid; titanium(IV) oxide at 20 - 30℃; for 10h; Electrochemical reaction;	75%

4-iodo-1-methyl-1H-pyrazole (39806-90-1) + diethyl pyridine-2,4-dicarboxylate (41438-38-4) → ethyl 2-(1-methyl-1H-pyrazole-4-carbonyl)isonicotinate

Conditions	Yield
Stage #1: 4-iodo-1-methyl-1H-pyrazole With isopropylmagnesium chloride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: diethyl pyridine-2,4-dicarboxylate In tetrahydrofuran at -78 - 20℃;	21%

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2,4-pyridinedicarboxylic acid dihydrazide (21379-40-8)

Conditions	Yield
With ethanol; hydrazine hydrate
With hydrazine hydrate In ethanol

octanol (111-87-5) + diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2-ethyl-4-octyl pyridinedicarboxylate + 2-octyl-4-ethyl pyridinedicarboxylate + 2,4-dioctyl pyridinedicarboxylate

Conditions	Yield
With 4 A molecular sieve; Mucor miehei lipase In di-isopropyl ether at 60℃; for 240h; Product distribution; regioselectivity of catalyzed transesterification of several aromatic and heteroaromatic substrates;
With 4 A molecular sieve; Mucor miehei lipase In di-isopropyl ether at 60℃;
With 4 A molecular sieve; Mucor miehei lipase In di-isopropyl ether at 60℃; for 240h;	A n/a B n/a C 80 % Chromat.

octanol (111-87-5) + diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2-octyl-4-ethyl pyridinedicarboxylate

Conditions	Yield
With 4 A molecular sieve In di-isopropyl ether at 60℃; for 240h;	83 % Chromat.

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2,4-bis[2-(4-tert-butylphennyl)-1,3,4-oxadiazol-5-yl]pyridine

Conditions	Yield
Multi-step reaction with 3 steps 1: N2H4*H2O / ethanol 2: 99 percent / pyridine / 1 h / Heating 3: 46 percent / POCl3 View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 4-[N'-(4-tert-butyl-benzoyl)-hydrazinocarbonyl]-pyridine-2-carboxylic acid N'-(4-tert-butyl-benzoyl)-hydrazide

Conditions	Yield
Multi-step reaction with 2 steps 1: N2H4*H2O / ethanol 2: 99 percent / pyridine / 1 h / Heating View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2,4-diethylpiperidine (116435-88-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 7 percent / TiO2; 35 percent aq. H2SO4 / 10 h / 20 - 30 °C / Electrochemical reaction View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2,4-diethylpyridine (626-21-1) + 2-ethyl-pyridin; 4-ethyl-pyridine

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 50 percent / TiO2; 35 percent aq. H2SO4 / 10 h / 20 - 30 °C / Electrochemical reaction View Scheme
Multi-step reaction with 3 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 26 percent / TiO2; 35 percent aq. H2SO4 / 10 h / 20 - 30 °C / Electrochemical reaction 3.1: 71 percent / Zn; 80 percent HCOOH / 10 h / 160 - 165 °C View Scheme
Multi-step reaction with 3 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 14 percent / Zn; 80 percent HCOOH / 10 h / 160 - 165 °C 3.1: 65 percent / Zn; 80 percent HCOOH / 10 h / 160 - 165 °C View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2,4-diethyl-1,2,5,6-tetrahydropyridine

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 15 percent / TiO2; 35 percent aq. H2SO4 / 10 h / 20 - 30 °C / Electrochemical reaction View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2,4-di-(1'-hydroxyethyl)pyridine (244610-88-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 26 percent / TiO2; 35 percent aq. H2SO4 / 10 h / 20 - 30 °C / Electrochemical reaction View Scheme
Multi-step reaction with 3 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 14 percent / Zn; 80 percent HCOOH / 10 h / 160 - 165 °C 3.1: 68 percent / ZnHgCl2; conc. HCl / 9 h / 160 - 165 °C View Scheme
Multi-step reaction with 3 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 14 percent / ZnHgCl2; conc. HCl / 9 h / 160 - 165 °C 3.1: 68 percent / ZnHgCl2; conc. HCl / 9 h / 160 - 165 °C View Scheme
Multi-step reaction with 2 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 51 percent / ZnHgCl2; conc. HCl / 9 h / 160 - 165 °C View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2-(1'-hydroxyethyl)-4-acetylpyridine (185220-30-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 14 percent / Zn; 80 percent HCOOH / 10 h / 160 - 165 °C View Scheme
Multi-step reaction with 2 steps 1.1: NaOEt / ethyl acetate / 2 h / 70 - 80 °C 1.2: 88 percent / 1 N aq. HCl / ethyl acetate / 4 h / Heating 2.1: 14 percent / ZnHgCl2; conc. HCl / 9 h / 160 - 165 °C View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2-(hydroxyimino-methyl)-isonicotinic acid ethyl ester (10177-26-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: LiAlH4 / tetrahydrofuran / 1.33 h / -60 °C 2: NH2OH*HCl, NaHCO3 / H2O View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 4-Carboxy-2-(hydroxyimino-methyl)-1-methyl-pyridinium; iodide

Conditions	Yield
Multi-step reaction with 4 steps 1: LiAlH4 / tetrahydrofuran / 1.33 h / -60 °C 2: NH2OH*HCl, NaHCO3 / H2O 3: 70 percent / dimethylformamide / 12 h / 60 °C 4: NaOH, H2O View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 4-Ethoxycarbonyl-2-(hydroxyimino-methyl)-1-methyl-pyridinium; iodide

Conditions	Yield
Multi-step reaction with 3 steps 1: LiAlH4 / tetrahydrofuran / 1.33 h / -60 °C 2: NH2OH*HCl, NaHCO3 / H2O 3: 70 percent / dimethylformamide / 12 h / 60 °C View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2-difluoromethylisonicotinic acid ethyl ester (1192539-75-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -78 °C 1.2: 1.5 h / 20 °C 2.1: dichloromethane / 5 h / 0 - 20 °C View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → N-cyclopropyl-4-(hydroxymethyl)pyridine-2-carboxamide (332013-47-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: magnesium chloride / ethanol / 48 h / 0 - 20 °C 2: calcium chloride; sodium hydroxide; sodium tetrahydroborate; water / methanol; isopropyl alcohol / 20 °C View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → (4-(chloromethyl)pyridin-2-yl)-N-cyclopropylcarboxamide (1353657-40-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: magnesium chloride / ethanol / 48 h / 0 - 20 °C 2: calcium chloride; sodium hydroxide; sodium tetrahydroborate; water / methanol; isopropyl alcohol / 20 °C 3: thionyl chloride / 20 °C View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → ethyl 2-((1R,3R)-3-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)isonicotinate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 0.5 h / 0 °C 1.2: -78 - 20 °C 2.1: sodium acetate; tetraethoxy orthosilicate / dimethyl sulfoxide / 48 h / 92 °C View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → ethyl 2-((1S,3R)-3-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)isonicotinate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 0.5 h / 0 °C 1.2: -78 - 20 °C 2.1: sodium acetate; tetraethoxy orthosilicate / dimethyl sulfoxide / 48 h / 92 °C View Scheme

diethyl pyridine-2,4-dicarboxylate (41438-38-4) → 2-((1R,3R)-3-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)isonicotinic acid trifluoroacetate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: isopropylmagnesium chloride / tetrahydrofuran / 0.5 h / 0 °C 1.2: -78 - 20 °C 2.1: sodium acetate; tetraethoxy orthosilicate / dimethyl sulfoxide / 48 h / 92 °C 3.1: lithium hydroxide monohydrate; water / methanol / 2 h / 20 °C 4.1: dimethyl sulfoxide; acetonitrile; water View Scheme

Upstream product

• 499-80-9 pyridine-2,4-dicarboxylic acid 
• 64-17-5 ethanol 
• 110-86-1 pyridine 
• 617-35-6 2-oxo-propionic acid ethyl ester 
• 121-44-8 triethylamine 

Downstream Products

• 21908-08-7 ethyl 2-formylpyridine-4-carboxylate 
• 108-47-4 2,4-lutidine 
• 21071-04-5 2,4-Bis(hydroxymethyl)pyridin 
• 20857-17-4 2,4-diacetylpyridine 
• 185220-30-8 2-(1'-hydroxyethyl)-4-acetylpyridine 
• 1596348-32-1 KDM5-C70 
• 6220-65-1 pyridine-2,4-dicarbaldehyde 
• 31804-60-1 ethyl 2-(hydroxymethyl)pyridine-4-carboxylate 
• 212914-74-4 4-(hydroxymethyl)pyridine-2-carbaldehyde 

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