144689-94-1

Basic information

• Product Name: Diethyl 2-propylImidazoledicarbonate
• Synonyms: 2-PROPYL-1H-IMIDAZOLE-4,5-DICARBOXYL;2-Propylimidazoledicarboxylic acid diethyl ester;2-PROPYL-4,5-IMIDAZOLEDICARBOXYLIC ACID DIETHYL ESTER 98.0%;2-propyl-, diethyl ester;1H-Imidazole-4,5-dicarboxylic acid, 2-propyl-, 4,5-diethyl ester;2-proyl-4,5-imidazoledicarboxylic acid diethyl ester;4,5-diethyl 2-propyl-1H-iMidazole-4,5-dicarboxylate;2-Propyl-1H-iMidazole-4,5-dicarboxylic Acid 4,5-Diethyl Ester
• CAS NO: 144689-94-1
• Molecular Formula: C₁₂H₁₈N₂O₄
• Molecular Weight: 254.28
• EINECS: 1592732-453-0
• Product Categories: Pharmaceutical material and intermeidates;Organic acids;Aromatics;Intermediates
• Mol File: 144689-94-1.mol
• Article Data: 8

Chemical Properties

• Melting Point: 86 °C
• Boiling Point: 400.9 °C at 760 mmHg
• Flash Point: 196.2 °C
• Appearance: /
• Density: 1.16 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.512
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 9.25±0.10(Predicted)
• CAS DataBase Reference: Diethyl 2-propylImidazoledicarbonate(CAS DataBase Reference)
• NIST Chemistry Reference: Diethyl 2-propylImidazoledicarbonate(144689-94-1)
• EPA Substance Registry System: Diethyl 2-propylImidazoledicarbonate(144689-94-1)

Safety Data

• Hazardous Substances Data: 144689-94-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Diethyl 2-propylImidazoledicarbonate is used as a key intermediate in the synthesis of Olmesartan Medoxomil for the treatment of hypertension. Its role in the production process is crucial for creating an effective medication that helps manage blood pressure levels in patients.

InChI:InChI=1/C12H18N2O4/c1-4-7-8-13-9(11(15)17-5-2)10(14-8)12(16)18-6-3/h4-7H2,1-3H3,(H,13,14)

Synthetic route

2-propyl-1H-imidazole-4,5-dicarboxylic acid (58954-23-7) + ethanol (64-17-5) → 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1)

Conditions	Yield
Stage #1: 2-propyl-1H-imidazole-4,5-dicarboxylic acid; ethanol With hydrogenchloride; thionyl chloride at 5℃; for 0.166667h; Stage #2: for 1.5h; Heating;	94%
With hydrogenchloride Ambient temperature;	86%
With thionyl chloride In water at 8℃; for 6.6h; Temperature; Reflux;	77%
at 0℃; for 12h; Reflux;

diethyl 2,3-dioxosuccinate (59743-08-7) + butyraldehyde (123-72-8) → 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1)

Conditions	Yield
With ammonia In tetrahydrofuran at 30 - 70℃; for 6h;	85.5%
With ammonium acetate In tetrahydrofuran; acetic acid at 60℃; for 3h; Product distribution / selectivity; light-shielding conditions;

butylamidine hydrochloride (3020-81-3) + diethyl 3-chloro-2-oxosuccinate (34034-87-2) → 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1)

Conditions	Yield
With pyridine In propan-1-ol for 6h; Reagent/catalyst; Solvent; Reflux;	80%

2-propylimidazole-4,5-dicarbonitrile (51802-42-7) → 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / 6N aq. HCl / 8 h / Heating 2: 86 percent / HCl / Ambient temperature View Scheme

diethyl 2-propyl-1H-imidazole-4,5-dicarboxylate hydrochloride → 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1)

Conditions	Yield
With sodium chloride; sodium hydroxide In water for 1h; Cooling with ice;

methyl bromide (74-83-9) + 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate (144689-93-0)

Conditions	Yield
With iodine; magnesium In dichloromethane at 15 - 25℃; for 2h;	97.5%

methylmagnesium bromide (75-16-1) + 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate (144689-93-0)

Conditions	Yield
In diethyl ether; dichloromethane at 10 - 15℃; for 1h;	95%

methylmagnesium chloride (676-58-4) + 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate (144689-93-0)

Conditions	Yield
Stage #1: methylmagnesium chloride; diethyl 2-(n-propyl)-1H-imidazole-4,5-dicarboxylate In tetrahydrofuran at -10 - 0℃; for 0.166667h; Stage #2: With water; ammonium chloride In tetrahydrofuran; dichloromethane	85%
Stage #1: methylmagnesium chloride; diethyl 2-(n-propyl)-1H-imidazole-4,5-dicarboxylate In tetrahydrofuran; toluene for 6.5h; Inert atmosphere; Cooling with ice; Stage #2: With hydrogenchloride In tetrahydrofuran; water; toluene pH=7;
In tetrahydrofuran at 60℃; for 2h;	4.81 g

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 2-propyl-1H-imidazole-4,5-dicarboxylic acid (58954-23-7)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran at 50℃; for 4h;	85%

ethylmagnesium bromide (925-90-6) + 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 5-(1-Ethyl-1-hydroxy-propyl)-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester (172875-50-2)

Conditions	Yield
In diethyl ether; dichloromethane at 10 - 15℃; for 1h;	83%

methylene chloride (74-87-3) + 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate (144689-93-0)

Conditions	Yield
Stage #1: methylene chloride With magnesium In tetrahydrofuran for 0.5h; Reflux; Stage #2: diethyl 2-(n-propyl)-1H-imidazole-4,5-dicarboxylate In tetrahydrofuran at 30℃; for 2.5h; Solvent; Temperature;	80%
Stage #1: methylene chloride With magnesium at 55 - 60℃; for 1h; Inert atmosphere; Stage #2: diethyl 2-(n-propyl)-1H-imidazole-4,5-dicarboxylate at 0℃; for 8h;

4'-bromomethyl-biphenyl-2-carboxylic acid tert-butyl ester (114772-40-6) + 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → diethyl 1-[(2'-t-butoxycarbonylbiphenyl-4-yl)methyl]-2-propylimidazole-4,5-dicarboxylate (144690-85-7)

Conditions	Yield
With potassium tert-butylate 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h; Yield given. Multistep reaction;

N-(triphenylmethyl)-5-<4'-(bromomethyl)biphenyl-2-yl>tetrazole (133051-88-4) + 2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 2-Propyl-1-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-imidazole-4,5-dicarboxylic acid diethyl ester (172875-56-8)

Conditions	Yield
With potassium tert-butylate 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h; Yield given. Multistep reaction;

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) POCl3, 2.) pyridine / 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → ethyl 4-isopropyl-2-propylimidazole-5-carboxylate (172875-51-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) POCl3, 2.) pyridine / 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h 3: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-methyl-2-propyl-3H-imidazole-4-carboxylic acid

Conditions	Yield
Multi-step reaction with 6 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 82 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 20 h / -5 °C 3: 100 percent / Et3N / CH2Cl2 / 0.5 h / Ambient temperature 4: 61 percent / Bu3SnH, 2,2'-azobis(isobutyronitrile) / toluene / 1.5 h / Heating 5: 89 percent / HCl / dioxane / 16 h / Ambient temperature 6: 94 percent / NaOH / dioxane; H2O / 5 h / 70 °C View Scheme
Multi-step reaction with 6 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: LiAlH(O-t-Bu)3 / tetrahydrofuran / 120 h / Ambient temperature 3: 100 percent / Et3N / CH2Cl2 / 0.5 h / Ambient temperature 4: 61 percent / Bu3SnH, 2,2'-azobis(isobutyronitrile) / toluene / 1.5 h / Heating 5: 89 percent / HCl / dioxane / 16 h / Ambient temperature 6: 94 percent / NaOH / dioxane; H2O / 5 h / 70 °C View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-isopropyl-2-propyl-3H-imidazole-4-carboxylic acid

Conditions

Yield

Multi-step reaction with 6 steps 1: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) POCl3, 2.) pyridine / 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h 3: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature 4: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 5: 82 percent / HCl / dioxane / 16 h / Ambient temperature 6: 100 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-isopropenyl-2-propyl-3H-imidazole-4-carboxylic acid

Conditions	Yield
Multi-step reaction with 5 steps 1: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) POCl3, 2.) pyridine / 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h 3: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 4: 92 percent / HCl / dioxane / 16 h / Ambient temperature 5: 94 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → ethyl 1-<(2'-carboxybiphenyl-4-yl)methyl>-4-methyl-2-propylimidazole-5-carboxylate (172876-10-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 82 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 20 h / -5 °C 3: 100 percent / Et3N / CH2Cl2 / 0.5 h / Ambient temperature 4: 61 percent / Bu3SnH, 2,2'-azobis(isobutyronitrile) / toluene / 1.5 h / Heating 5: 89 percent / HCl / dioxane / 16 h / Ambient temperature View Scheme
Multi-step reaction with 5 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: LiAlH(O-t-Bu)3 / tetrahydrofuran / 120 h / Ambient temperature 3: 100 percent / Et3N / CH2Cl2 / 0.5 h / Ambient temperature 4: 61 percent / Bu3SnH, 2,2'-azobis(isobutyronitrile) / toluene / 1.5 h / Heating 5: 89 percent / HCl / dioxane / 16 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 1-(2'-Carboxy-biphenyl-4-ylmethyl)-5-hydroxymethyl-2-propyl-1H-imidazole-4-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 66 percent / LiAlH(O-t-Bu)3 / tetrahydrofuran / 120 h / Ambient temperature 3: 100 percent / HCl / dioxane / 16 h / Ambient temperature 4: 100 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-hydroxymethyl-2-propyl-3H-imidazole-4-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 82 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 20 h / -5 °C 3: 93 percent / HCl / dioxane / 16 h / Ambient temperature 4: 96 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme
Multi-step reaction with 4 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: LiAlH(O-t-Bu)3 / tetrahydrofuran / 120 h / Ambient temperature 3: 93 percent / HCl / dioxane / 16 h / Ambient temperature 4: 96 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 1-[(2’-carboxybiphenyl-4-yl)methyl]-2-propylimidazole-4,5-dicarboxylic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 96 percent / HCl / dioxane / 16 h / Ambient temperature 3: 100 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 4'-(4,5-Bis-hydroxymethyl-2-propyl-imidazol-1-ylmethyl)-biphenyl-2-carboxylic acid tert-butyl ester (154237-82-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 66 percent / LiAlH(O-t-Bu)3 / tetrahydrofuran / 120 h / Ambient temperature 3: 77 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 20 h / -5 °C View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-isopropyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester (172875-76-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) POCl3, 2.) pyridine / 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h 3: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature 4: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 5: 82 percent / HCl / dioxane / 16 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-isopropenyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester (172875-80-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) POCl3, 2.) pyridine / 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h 3: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 4: 92 percent / HCl / dioxane / 16 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-hydroxymethyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester (154237-91-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 82 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 20 h / -5 °C 3: 93 percent / HCl / dioxane / 16 h / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: LiAlH(O-t-Bu)3 / tetrahydrofuran / 120 h / Ambient temperature 3: 93 percent / HCl / dioxane / 16 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 5-Methyl-2-propyl-3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid

Conditions	Yield
Multi-step reaction with 6 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 69 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 20 h / -5 °C 3: Et3N / CH2Cl2 / 0.5 h / Ambient temperature 4: 87 percent / Bu3SnH, 2,2'-azobis(isobutyronitrile) / toluene / 1.5 h / Heating 5: 96 percent / 25percent aq. AcOH / 2.5 h / 80 °C 6: 97 percent / NaOH / dioxane; H2O / 5 h / 70 °C View Scheme
Multi-step reaction with 6 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: LiAlH(O-t-Bu)3 / tetrahydrofuran / 192 h 3: Et3N / CH2Cl2 / 0.5 h / Ambient temperature 4: 87 percent / Bu3SnH, 2,2'-azobis(isobutyronitrile) / toluene / 1.5 h / Heating 5: 96 percent / 25percent aq. AcOH / 2.5 h / 80 °C 6: 97 percent / NaOH / dioxane; H2O / 5 h / 70 °C View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 3: 92 percent / HCl / dioxane / 16 h / Ambient temperature 4: 91 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 3-(2'-tert-Butoxycarbonyl-biphenyl-4-ylmethyl)-5-methyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester (172876-05-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 82 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 20 h / -5 °C 3: 100 percent / Et3N / CH2Cl2 / 0.5 h / Ambient temperature 4: 61 percent / Bu3SnH, 2,2'-azobis(isobutyronitrile) / toluene / 1.5 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: LiAlH(O-t-Bu)3 / tetrahydrofuran / 120 h / Ambient temperature 3: 100 percent / Et3N / CH2Cl2 / 0.5 h / Ambient temperature 4: 61 percent / Bu3SnH, 2,2'-azobis(isobutyronitrile) / toluene / 1.5 h / Heating View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → XF 818

Conditions

Yield

Multi-step reaction with 6 steps 1: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) POCl3, 2.) pyridine / 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h 3: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature 4: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 5: 93 percent / 25percent aq. AcOH / 2.5 h / 80 °C 6: 89 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-4-(prop-1-en-2-yl)-2-propyl-1H-imidazole-5-carboxylic acid

Conditions	Yield
Multi-step reaction with 5 steps 1: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) POCl3, 2.) pyridine / 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h 3: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 4: 94 percent / 25percent aq. AcOH / 2.5 h / 80 °C 5: 85 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

2-propyl-1H-imidazole-4, 5-diethyl azodicarboxylate (144689-94-1) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-(1-ethyl-1-hydroxy-propyl)-2-propyl-3H-imidazole-4-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1: 83 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 2: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 3: 92 percent / HCl / dioxane / 16 h / Ambient temperature 4: 95 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

Upstream product

• 3020-81-3 butylamidine hydrochloride 
• 34034-87-2 diethyl 3-chloro-2-oxosuccinate 
• 59743-08-7 diethyl 2,3-dioxosuccinate 
• 123-72-8 butyraldehyde 
• 51802-42-7 2-propylimidazole-4,5-dicarbonitrile 
• 58954-23-7 2-propyl-1H-imidazole-4,5-dicarboxylic acid 
• 64-17-5 ethanol 

Downstream Products

• 144689-93-0 ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate 
• 144690-96-0 1-[{2'-cyanobiphenyl-4-yl}methyl]-4-(1-hydroxy-1-methylethyl)-2-propylimidazol-5-carboxylic acid ethyl ester 
• 1199807-37-8 diethyl 1-(2'-cyanobiphenyl-4-yl)methyl-2-propyl-1H-imidazole-4,5-dicarboxylate 
• 58954-23-7 2-propyl-1H-imidazole-4,5-dicarboxylic acid 
• 1378863-69-4 ethyl 4-(1-hydroxy-1-methylpropyl)-2-propyl-1-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H-imidazole-5-carboxylate 
• 1378863-74-1 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(1-hydroxy-1-methylpropyl)-2-propyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylate 
• 1378863-72-9 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(1-hydroxy-1-methylpropyl)-2-propyl-1-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H-imidazole-5-carboxylate 
• 172875-53-5 ethyl 4-(1-hydroxy-1-methylpropyl)-2-propylimidazole-5-carboxylate 
• 144690-53-9 2-propyl-1-[2'-(1-triphenylmethyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-imidazole-4,5-dicarboxylic acid diethyl ester 
• 144689-92-9 ethyl 2-butyl-4-(1-hydroxy-1-methylethyl)imidazole-5-carboxylate 
• 1020157-01-0 (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl4-(1-hydroxy-1-methylethyl)-2-propyl-1-[2′-(2-triphenylmethyl-2H-tetrazol-5-yl)biphenyl-4-yl]methyl-1H-imidazole-5-carboxylate 
• 1027174-22-6 5-(1-Hydroxy-1-methyl-ethyl)-2-propyl-3-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid 2,2-dimethyl-propionyloxymethyl ester 
• 172876-04-9 5-Hydroxymethyl-2-propyl-1-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-imidazole-4-carboxylic acid ethyl ester 
• 172875-70-6 5-Isopropenyl-2-propyl-3-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid ethyl ester 

Relevant articles and documents

Preparation method of 2-propyl-4, 5-imidazole diethyl dicarboxylate

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of 2-propyl-4, 5-imidazole diethyl dicarboxylate, which comprises the following steps: by using L-tartaric acid as an initial raw material, carrying out esterification reaction, oxidation reaction and cyclization reaction to obtain the 2-propyl-4, 5-imidazole diethyl dicarboxylate product. A one-pot method is adopted for preparation, the method is simple, safety is good, and industrial production is easy to implement; the method has the advantages of mild reaction conditions, less three wastes, simple distillation and recycling of the solvent, simple process, low cost, high product purity and high yield compared with the existing process.

Synthesis method of olmesartan intermediate

The invention relates to the field of drug intermediate synthesis, in particular to a synthesis method of an olmesartan intermediate, which is characterized in that tartaric acid is used as a raw material, and the olmesartan intermediate is prepared by cyclization reaction, esterification reaction and methylation reaction. According to the synthesis method of the olmesartan intermediate, the totalyield can reach 60% or above, the yield is high, and economic benefits are high; the synthesis route is simple, basic raw materials are cheaper, side reactions are few, and purification is easy; andthe whole steps are easy to control, the method is more suitable for industrial application from raw materials to production, selection of ingredients and determination of the addition amount, and theproduction cost is low.

A 4 - (1 - hydroxy -1 - methyl ethyl) -2 - propyl - 1H - imidazole -5 - carboxylic acid ethyl ester preparation method

The invention relates to a preparation method of 4-(1-hydroxy-1-methyl ethyl)-2-propyl-1H-imidazole-5-carboxylic acid ethyl ester and belongs to the technical field of medicament synthesis. In order to solve the problems of long reaction route, heavy pollution and low yield in the prior art, the invention provides a preparation method of 4-(1-hydroxy-1-methyl ethyl)-2-propyl-1H-imidazole-5-carboxylic acid ethyl ester. The method comprises the following steps: in the presence of organic alkali, enabling a raw material alpha-chlorinated oxaloacetic acid diethyl ester to react with butanimidamide or acidic salt of butanimidamide to obtain an intermediate compound, then enabling the intermediate compound to perform Grignard reaction with CH3MgX to obtain 4-(1-hydroxy-1-methyl ethyl)-2-propyl-1H-imidazole-5-carboxylic acid ethyl ester, wherein X in CH3MgX is halogen. The method disclosed by the invention has the advantages of short reaction route, less pollution, mild reaction condition and high yield.

2-aminoalkylimidazole -4, 5-dicarboxilic manufacturing method

PROBLEM TO BE SOLVED: To provide a method for producing inexpensively with a high yield, 2-alkylimidazole-4,5-dicarboxylic acid which is useful as a medicinal intermediate. SOLUTION: In this method for producing 2-alkylimidazole-4,5-dicarboxylic acid, tartaric acid is dissolved into nitric acid and then reacted with concentrated sulfuric acid, and a nitrate of tartaric acid acquired by the reaction is added into a solvent containing at least one kind of organic solvent selected from among N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, methylcyclohexane and toluene. Thereafter, a mixed liquid of aldehyde and ammonia is added to the reaction liquid, to thereby produce 2-alkylimidazole-4,5-dicarboxylic acid. COPYRIGHT: (C)2012,JPOandINPIT

METHOD FOR PRODUCING 1-BIPHENYLMETHYLIMIDAZOLE COMPOUND

The present invention provides a method for producing a 1-biphenylmethylimidazole compound having superior angiotensin II receptor antagonistic activity, or an intermediate thereof. The present invention provides a method for producing a compound having the formula (5) (R1 , Ra : H, an alkyl group) by oxidizing a compound having the formula (1) (R a : H, an alkyl group) using an oxidizing agent in the presence of a radical initiation reagent, and then reacting with an ammonia-generating reagent and a compound having the formula R 1 CHO (R 1 : H, an alkyl group) or a compound having the formula R1C(ORb)3 (R1: H,an alkyl group; Rb : an alkyl group).

ANGIOTENSIN II ANTAGONIST 1-BIPHENYLMETHYLIMIDAZOLE COMPOUNDS AND THEIR THERAPEUTIC USE

Compounds of the following formula (I) or the formula (I) p : STR1 wherein R 1 is alkyl or alkenyl; R 2 and R 3 are hydrogen, alkyl, alkenyl, cycloalkyl, aralkyl, aryl, or aryl fused to cycloalkyl; R 4 is hydrogen, alkyl, alkanoyl, alkenoyl, arylcarbonyl, alkoxycarbonyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, tetrahydrofuryl, a group of formula--SiR a R b R c, in which R a, R b and R c are alkyl or aryl, alkoxymethyl, (alkoxyalkoxy)methyl, haloalkoxymethyl, aralkyl, aryl or alkanoyloxymethoxycarbonyl; R 5 is carboxy or--CONR 8 R 9, wherein R 8 and R 9 hydrogens or alkyl, or R 8 and R 9 together form alkylene; R 6 is hydrogen, alkyl, alkoxy or halogen; R. sup.7 is carboxy or tetrazol-5-yl; R p. sup.1 is hydrogen, alkyl, cycloalkyl or alkanoyl; R p 2 is a single bond, alkylene or alkylidene; R p 3 and R p 4 are each hydrogen or alkyl; R. sub.p 6 is carboxy or tetrazol-5-yl; and X p is oxygen or sulfur; and pharmaceutically acceptable salts and esters thereof. The compounds are AII receptor antagonists and thus have hypotensive activity and can be used for the treatment and prophylaxis of hypertension. The compounds may be prepared by reacting a biphenylmethyl compound with an imidazole compound.

Nonpeptide angiotensin II receptor antagonists: Synthesis, biological activities, and structure - Activity relationships of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds

A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)-imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)-methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2′-1H-tetrazol-5-ylbiphenyl-4-yl) -methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken.