157356-73-5

Basic information

• Product Name: 4-(1-Methylethenyl)-2-propyl-1H-Imidazole-5-carboxylic acidethylester
• Synonyms: 4-(1-Methylethenyl)-2-propyl-1H-Imidazole-5-carboxylic acidethylester;5-(1-Methylethenyl)-2-propyl-1H-iMidazole-4-carboxylic Acid Ethyl Ester;ethyl 4-(prop-1-en-2-yl)-2-propyl-1H-iMidazole-5-carboxylate;OlMesartan interMediate iMpurity VI;Ethyl-4-(Prop-1-en-2-yl)-2-propyl;Olmesartan intermediate impurity Ⅳ;Olmesartan Impurity 8;1H-Imidazole-5-carboxylic acid, 4-(1-methylethenyl)-2-propyl-, ethyl ester
• CAS NO: 157356-73-5
• Molecular Formula: C₁₂H₁₈N₂O₂
• Molecular Weight: 222.28352
• Product Categories: Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 157356-73-5.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 411.9±33.0 °C(Predicted)
• Appearance: /
• Density: 1.055±0.06 g/cm3(Predicted)
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly)
• PKA: 11.01±0.10(Predicted)
• CAS DataBase Reference: 4-(1-Methylethenyl)-2-propyl-1H-Imidazole-5-carboxylic acidethylester(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(1-Methylethenyl)-2-propyl-1H-Imidazole-5-carboxylic acidethylester(157356-73-5)
• EPA Substance Registry System: 4-(1-Methylethenyl)-2-propyl-1H-Imidazole-5-carboxylic acidethylester(157356-73-5)

Safety Data

• Hazardous Substances Data: 157356-73-5(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Olmesartan intermediate.

Synthetic route

ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate (144689-93-0) → ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5)

Conditions	Yield
With pyridine; trichlorophosphate 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h; Yield given. Multistep reaction;

2-propyl-1H-imidazole-4,5-dicarboxylic acid (58954-23-7) → ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 86 percent / HCl / Ambient temperature 2: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 3: 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-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-propylimidazole-4,5-dicarbonitrile (51802-42-7) → ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 80 percent / 6N aq. HCl / 8 h / Heating 2: 86 percent / HCl / Ambient temperature 3: 95 percent / diethyl ether; CH2Cl2 / 1 h / 10 - 15 °C 4: 1.) POCl3, 2.) pyridine / 1.) benzene, reflux, 1 h, 2.) benzene, reflux, 1 h View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → ethyl 4-isopropyl-2-propylimidazole-5-carboxylate (172875-51-3)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol for 3h; Ambient temperature;	93%

4'-bromomethyl-biphenyl-2-carboxylic acid tert-butyl ester (114772-40-6) + ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 3-(2'-tert-Butoxycarbonyl-biphenyl-4-ylmethyl)-5-isopropenyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester (172875-64-8) + 1-(2'-tert-Butoxycarbonyl-biphenyl-4-ylmethyl)-5-isopropenyl-2-propyl-1H-imidazole-4-carboxylic acid ethyl ester

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

N-(triphenylmethyl)-5-<4'-(bromomethyl)biphenyl-2-yl>tetrazole (133051-88-4) + ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 5-Isopropenyl-2-propyl-1-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-imidazole-4-carboxylic acid ethyl ester + 5-Isopropenyl-2-propyl-3-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid ethyl ester (172875-70-6)

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

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-isopropyl-2-propyl-3H-imidazole-4-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature 2: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 3: 82 percent / HCl / dioxane / 16 h / Ambient temperature 4: 100 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-isopropenyl-2-propyl-3H-imidazole-4-carboxylic 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: 92 percent / HCl / dioxane / 16 h / Ambient temperature 3: 94 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 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 3 steps 1: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature 2: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 3: 82 percent / HCl / dioxane / 16 h / Ambient temperature View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 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 2 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 92 percent / HCl / dioxane / 16 h / Ambient temperature View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → XF 818

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature 2: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 3: 93 percent / 25percent aq. AcOH / 2.5 h / 80 °C 4: 89 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 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 3 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 94 percent / 25percent aq. AcOH / 2.5 h / 80 °C 3: 85 percent / LiOH*H2O / dioxane; H2O / 5 h / Ambient temperature View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 3-(2'-tert-Butoxycarbonyl-biphenyl-4-ylmethyl)-5-isopropyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester (172875-54-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature 2: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 5-Isopropyl-2-propyl-3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid ethyl ester (172875-85-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature 2: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 3: 93 percent / 25percent aq. AcOH / 2.5 h / 80 °C View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 5-Isopropenyl-2-propyl-3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid ethyl ester (172875-87-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h 2: 94 percent / 25percent aq. AcOH / 2.5 h / 80 °C View Scheme

ethyl 4-isopropenyl-2-propylimidazole-5-carboxylate (157356-73-5) → 5-Isopropyl-2-propyl-3-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid ethyl ester (172875-61-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / H2 / 10percent Pd/C / methanol / 3 h / Ambient temperature 2: 1.) t-BuOK / 1.) DMA, 0 deg C, 10 min, 2.) DMA, RT, 1 h View Scheme

Upstream product

• 144689-93-0 ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate 
• 58954-23-7 2-propyl-1H-imidazole-4,5-dicarboxylic acid 
• 144689-94-1 diethyl 2-(n-propyl)-1H-imidazole-4,5-dicarboxylate 
• 51802-42-7 2-propylimidazole-4,5-dicarbonitrile 

Downstream Products

• 172875-64-8 3-(2'-tert-Butoxycarbonyl-biphenyl-4-ylmethyl)-5-isopropenyl-2-propyl-3H-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 
• 172875-76-2 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-isopropyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester 
• 172875-80-8 3-(2'-Carboxy-biphenyl-4-ylmethyl)-5-isopropenyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester 
• 172875-98-8 1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-4-(prop-1-en-2-yl)-2-propyl-1H-imidazole-5-carboxylic acid 
• 172875-54-6 3-(2'-tert-Butoxycarbonyl-biphenyl-4-ylmethyl)-5-isopropyl-2-propyl-3H-imidazole-4-carboxylic acid ethyl ester 
• 172875-85-3 5-Isopropyl-2-propyl-3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid ethyl ester 
• 172875-87-5 5-Isopropenyl-2-propyl-3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid ethyl ester 
• 172875-61-5 5-Isopropyl-2-propyl-3-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazole-4-carboxylic acid ethyl ester 

Relevant articles and documents

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.