124750-99-8

Basic information

• Product Name: Losartan potassium
• Synonyms: 2-BUTYL-4-CHLORO-1-[[2'-(1H-TETRAZOL-5YL)[1,1'-BIPHENYL]-4-YL]METHYL]-1H-IMIDAZOLE-5-METHANOL;2-butyl-4-chloro-1-[[2'-(1h-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1h-imidazole-5-methanol monopotassium salt;2-BUTYL-4-CHLORO-1-[[2'-(1H-TETRAZOLE-5-YL)[1,1'-BIPHENYL]-4-YL]METHYL]-1H-IMIDAZOLE-5-METHANOL, POTASSIUM SALT;COZAAR;DUP 753;LOSARTAN MONOPOTASSIUM SALT;LOSARTAN POTASSIUM;LOSARTAN POTASSIUM SALT
• CAS NO: 124750-99-8
• Molecular Formula: C₂₂H₂₂ClN₆O*K
• Molecular Weight: 462.01
• EINECS: 200-287-4
• Product Categories: Hypertension;Intermediates & Fine Chemicals;Pharmaceuticals;Losartan;APIS;Aromatics;Heterocycles;API Reference Standard;COZAAR;Cardiovascular APIs;API
• Mol File: 124750-99-8.mol

Chemical Properties

• Melting Point: 263-265°C
• Boiling Point: 682 °C at 760mmHg
• Flash Point: 366.3 °C
• Appearance: white to off-white crystalline powder
• Density: 0.986g/mLat 25°C(lit.)
• Vapor Pressure: 1.55E-19mmHg at 25°C
• Storage Temp.: Desiccate at RT
• Solubility: Freely soluble in water and in methanol, slightly soluble in acetonitrile.
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
• Merck: 14,5583
• BRN: 5845770
• CAS DataBase Reference: Losartan potassium(CAS DataBase Reference)
• NIST Chemistry Reference: Losartan potassium(124750-99-8)
• EPA Substance Registry System: Losartan potassium(124750-99-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• WGK Germany: 3
• RTECS: NI6755100
• Hazardous Substances Data: 124750-99-8(Hazardous Substances Data)

Usage

References

Different sources of media describe the References of 124750-99-8 differently. You can refer to the following data:
1. https://en.wikipedia.org/wiki/Losartan https://www.drugbank.ca/drugs/DB00678 https://pubchem.ncbi.nlm.nih.gov/compound/11751549#section=Top http://www.medicinenet.com/losartan-oral/article.htm
2. 1) Merck 14:5583 2) Chiu et al. (1990), Nonpeptide angiotensin II receptor antagonists. VII. Cellular and biochemical pharmacology of DuP 753, an orally active antihypertensive agent; J. Pharmacol. Exp. Ther., 252 711 3) McIntyre et al. (1997), Losartan, an orally active angiotensin (AT1) receptor antagonist: a review of it’s efficacy and safety in essential hypertension; Pharmacol. Ther., 74 181 4) Diop-Frimpong et al. (2011), Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors; Proc. Natl. Acad. Sci. USA, 108 2909 5) Pantazi et al. (2015), Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation; World J. Gastroenterol., 21 8021 6) Kumar et al. (2015), Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress; Inflammopharmacology, 23 291 7) Miguel-Carrasco et al. (2017), Mechanisms underlying the cardiac antifibrotic effects of losartan metabolites; Sci. Rep. 7 41865

Chemical Properties

White to Off-White Crystalline Powder

Originator

DuPont Merck (U.S.A.)

Uses

Different sources of media describe the Uses of 124750-99-8 differently. You can refer to the following data:
1. A nonpeptide angiotensin II AT1-receptor antagonist. Antihypertensive.
2. antihypertensive, AT1 angiotensin II antagonist
3. Coronary vasodilator used in the diagnosis of coronary heart disease (adenosine A2A agonist).

Therapeutic Function

Antihypertensive

Biological Activity

Selective non-peptide angiotensin AT 1 receptor antagonist. Inhibits the contractile effects of angiotensin II on rabbit aorta and jugular vein (pA 2 = 8.27). Orally active antihypertensive agent.

Clinical Use

#N/A

Drug interactions

Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Analgesics: antagonism of hypotensive effect and increased risk of renal impairment with NSAIDs; hyperkalaemia with ketorolac and other NSAIDs. Antihypertensives: increased risk of hyperkalaemia, hypotension and renal impairment with ACE-Is and aliskiren. Ciclosporin: increased risk of hyperkalaemia and nephrotoxicity. Diuretics: enhanced hypotensive effect; hyperkalaemia with potassium-sparing diuretics. ESAs: increased risk of hyperkalaemia; antagonism of hypotensive effect. Lithium: reduced excretion (possibility of enhanced lithium toxicity). Potassium salts: increased risk of hyperkalaemia. Tacrolimus: increased risk of hyperkalaemia and nephrotoxicity.

InChI:InChI=1/C22H22ClN6O.K/c1-2-3-8-20-24-21(23)19(14-30)29(20)13-15-9-11-16(12-10-15)17-6-4-5-7-18(17)22-25-27-28-26-22;/h4-7,9-12H,2-3,8,13-14H2,1H3,(H,25,26,27,28);/q-1;+1

Synthetic route

lorsartan (114798-26-4) → losartan potassium (124750-99-8)

Conditions	Yield
With potassium hydroxide In methanol; isopropyl alcohol at 20℃; for 0.5h;	90%
With potassium hydroxide In methanol for 4h; Heating / reflux;	33%
With potassium hydroxide In methanol for 1h; pH=9; Reflux;

2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)methyl]imidazole-5-carboxaldehyde (124750-67-0) → losartan potassium (124750-99-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate / methanol; N,N-dimethyl acetamide / 1 h / 5 - 20 °C 2.1: sodium azide; triethylamine hydrochloride / N,N-dimethyl acetamide / 16 h / 120 °C 2.2: 80 °C / pH 4.0 3.1: potassium hydroxide / methanol; isopropyl alcohol / 0.5 h / 20 °C View Scheme

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → losartan potassium (124750-99-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl acetamide / 5 h / 20 °C 2.1: sodium tetrahydroborate / methanol; N,N-dimethyl acetamide / 1 h / 5 - 20 °C 3.1: sodium azide; triethylamine hydrochloride / N,N-dimethyl acetamide / 16 h / 120 °C 3.2: 80 °C / pH 4.0 4.1: potassium hydroxide / methanol; isopropyl alcohol / 0.5 h / 20 °C View Scheme

4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile (114772-54-2) → losartan potassium (124750-99-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / N,N-dimethyl acetamide / 5 h / 20 °C 2.1: sodium tetrahydroborate / methanol; N,N-dimethyl acetamide / 1 h / 5 - 20 °C 3.1: sodium azide; triethylamine hydrochloride / N,N-dimethyl acetamide / 16 h / 120 °C 3.2: 80 °C / pH 4.0 4.1: potassium hydroxide / methanol; isopropyl alcohol / 0.5 h / 20 °C View Scheme

2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)-methyl]-5-(hydroxymethyl)imidazole (114772-55-3) → losartan potassium (124750-99-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium azide; triethylamine hydrochloride / N,N-dimethyl acetamide / 16 h / 120 °C 1.2: 80 °C / pH 4.0 2.1: potassium hydroxide / methanol; isopropyl alcohol / 0.5 h / 20 °C View Scheme

losartan potassium (124750-99-8) → 2-butyl-4-chloro-1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylic acid (124750-92-1)

Conditions	Yield
Stage #1: losartan potassium With pyridine; potassium permanganate; tetrabutyl-ammonium chloride In water; acetone at 40 - 50℃; for 1h; Stage #2: With hydrogenchloride In water; acetone Product distribution / selectivity;	72%
Stage #1: losartan potassium With potassium hydroxide In water at 2℃; for 2h; Stage #2: With sodium periodate; ruthenium trichloride In water at 4 - 6.5℃; for 19h;

trityl chloride (76-83-5) + losartan potassium (124750-99-8) → 2-Butyl-4-chloro-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol (124751-00-4)

Conditions	Yield
With triethylamine In dichloromethane; water

cis-Pt(ethylenediamine)nitrate-chloride (468724-95-0) + losartan potassium (124750-99-8) → losartan-cisULS

Conditions	Yield
In N,N-dimethyl-formamide at 60℃; for 72h;

losartan potassium (124750-99-8) → 2-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole-5-carboxylic acid monohydrate (913611-27-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium hydroxide / water / 2 h / 2 °C 1.2: 19 h / 4 - 6.5 °C 2.1: hydrogenchloride / acetic acid 3.1: water / 72 h / centrifuge tube View Scheme

Upstream product

• 124750-67-0 2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)methyl]imidazole-5-carboxaldehyde 
• 114772-54-2 4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile 
• 114772-53-1 2-Cyano-4'-methylbiphenyl 
• 114772-55-3 2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)-methyl]-5-(hydroxymethyl)imidazole 
• 155884-01-8 (2-(2H-tetrazol-5-yl)phenyl)boronic acid 
• 151012-31-6 2-n-Butyl-4-chloro-1-(4-bromobenzyl)-1H-imidazole-5-methanol 
• 67-56-1 methanol 
• 124751-00-4 2-Butyl-4-chloro-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol 
• 114798-26-4 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole 
• 133909-99-6 2-n-butyl-4-chloro-1-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)-1,1'-biphenyl-4-yl)methyl]-1H-imidazole-5-methanol 
• 114798-26-4 lorsartan 
• 1310-58-3 potassium hydroxide 
• 83857-96-9 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde 

Downstream Products

• 124751-00-4 2-Butyl-4-chloro-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol 
• 114798-26-4 lorsartan 
• 1034709-90-4 (2-butyl-4-chloro-1-{[2'-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methyl (5R)-5,6-bis(nitrooxy)hexanoate 
• 1228545-47-8 (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methyl (1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentanecarboxylate 
• 1186123-68-1 (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methyl 3-(nitrooxy)adamantane-1-carboxylate 
• 124750-92-1 2-butyl-4-chloro-1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylic acid 
• 114798-36-6 2-n-Butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole-5-carboxaldehyde 
• 913611-27-5 2-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole-5-carboxylic acid monohydrate 
• 1376614-91-3 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-butyl-4-chloro-1H-imidazole-5-carbaldehyde O-methyl oxime 
• 1370339-80-2 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-butyl-4-chloro-1H-imidazole-5-carbaldehyde oxime 
• 114798-36-6 EXP 3179 
• 727718-93-6 2-butyl-4-chloro-5-(azidomethyl)-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4yl)methyl]-1H-imidazole 

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