[ CAS No. 124750-92-1 ] {[proInfo.proName]}

Name: 124750-92-1|Losartan carboxylic acid|97%
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Quality Control of [ 124750-92-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 124750-92-1 ]

SDS Specification

Alternatived Products of [ 124750-92-1 ]

Product Details of [ 124750-92-1 ]

CAS No. :	124750-92-1	MDL No. :	MFCD00871928
Formula :	C₂₂H₂₁ClN₆O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZEUXAIYYDDCIRX-UHFFFAOYSA-N
M.W :	436.89	Pubchem ID :	108185
Synonyms :	E-3174;EXP-3174	Chemical Name :	Losartan carboxylic acid

Calculated chemistry of [ 124750-92-1 ]

Physicochemical Properties

Num. heavy atoms :	31
Num. arom. heavy atoms :	22
Fraction Csp3 :	0.23
Num. rotatable bonds :	8
Num. H-bond acceptors :	6.0
Num. H-bond donors :	2.0
Molar Refractivity :	117.94
TPSA :	109.58 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-5.37 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.22
Log Po/w (XLOGP3) :	5.07
Log Po/w (WLOGP) :	4.47
Log Po/w (MLOGP) :	3.58
Log Po/w (SILICOS-IT) :	4.49
Consensus Log Po/w :	3.97

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-5.74
Solubility :	0.000795 mg/ml ; 0.00000182 mol/l
Class :	Moderately soluble
Log S (Ali) :	-7.11
Solubility :	0.0000336 mg/ml ; 0.000000077 mol/l
Class :	Poorly soluble
Log S (SILICOS-IT) :	-7.94
Solubility :	0.00000503 mg/ml ; 0.0000000115 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	3.0
Synthetic accessibility :	3.38

Safety of [ 124750-92-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 124750-92-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 124750-92-1 ]

[ 124750-92-1 ] Synthesis Path-Downstream 1~34

1
[ 124750-99-8 ]
[ 114798-36-6 ]
[ 124750-92-1 ]

Reference： [1]Tetrahedron Letters,2003,vol. 44,p. 1149 - 1152
[2]Tetrahedron Letters,2003,vol. 44,p. 1149 - 1152

2
[ 114798-26-4 ]
[ 124750-92-1 ]

Yield	Reaction Conditions	Operation in experiment
78%	With pyridine; potassium permanganate; tetrabutyl-ammonium chloride; In water; acetone; at 40 - 50℃; for 1h;Product distribution / selectivity;	To a 2000 ml three necked round bottom flask equipped with condenser, mechanical stirrer, and thermometer was added de-ionized water (250 ml), potassium permanganate (0.25 mol) and stirred for about 15 minutes. Tetrabutylammonium chloride (0.30 ml) was added in four portions in 20 minutes. After stirring vigorously for 30 minutes, pyridine (100 ml) and acetone (650 ml) were added and the reaction mixture stirred for another 30 minutes.The dark purple solution was transferred into a 2000 ml three necked flask equipped with condenser, mechanical stirrer, and thermometer. The solution was warmed up to an internal temperature 40 C. <strong>[114798-26-4]Losartan</strong> (0.1 ml) [QUESTION: What is the total amount by weight of <strong>[114798-26-4]Losartan</strong>?] was added into the reaction mixture in portions with continued stirring. The internal temperature of the reaction mixture was maintained below 50 C. After one hour, the reaction was completed. To the reaction mixture, was added 30% formaldehyde solution (200 ml) slowly with the temperature maintained below 50 C. The reaction mixture was stirred until the purple color disappeared. Brown precipitates were also formed.The contents of the reaction vessel were filtered. The brown solid was washed with 1.0 M NaOH (100 ml×3). The filtrate was almost colorless. The filtrate was concentrated on a rotary evaporator to about of the original volume and stirred with mechanical stirrer and cooled in ice bath. A 6 M HCl solution was added dropwise to reduce the pH of the mixture to about 2. White precipitates were formed during acidification. The precipitate was filtered, washed with de-ionized water, dried in the air and recrystallized in 2-propanol to give white solid of losartan 5-carboxylic acid (EXP-3174). Yield for the reaction was calculated at 78%.The potassium salt of <strong>[114798-26-4]Losartan</strong> was also used for the reaction. The yield was 72%. 1H NMR(DMSO-d6, 400 MHz): 7.64(d, 1H), 6.62(t, 1H), 7.55(t, 1H), 7.59(d, 1H), 7.07(d, 2H), 6.96(d, 2H), 5.62(s, 2H), 2.55(t, 2H), 1.51(q, 2H), 1.21(m, 2H), 0.85(t, 3H)
	With sodium periodate; ruthenium(III) trichloride hydrate; potassium hydroxide; In water; at 0℃;	Step A: Water (100 ml), potassium hydroxide (152.4 mmol) was added to a four-necked flask at 0 C followed by losartan (10.9 mmol) Sodium periodate (25.9 mmol) and ruthenium (III) chloride monohydrate (0.5 mmol) And the reaction mixture is added 0 C Under stirring overnight. The reaction mixture was filtered. Adding isopropyl alcohol to the filtrate in a stirred state, heating the solution to 25 C and stirring for 2.5 hours, adding phosphoric acid thereto, maintaining the temperature below 30 C. The mixture was stirred for 30 minutes and the resulting product was filtered, washed with water and the residue was dried in vacuo to give 2-butyl-4-chloro-1 - ((2 '- (1H-tetrazol- - [1,1'-biphenyl] -4-yl) methyl) -1H-imidazole-5-carboxylic acid.
		Step A: To the four-necked flask was added water (100 ml), potassium hydroxide (152.4 mmol) at 0 C, followed by the addition of chlorine(10.9 mmol), sodium periodate (25.9 mmol) and ruthenium (III) chloride monohydrate (0.5 mmol) were added and the reaction mixture was stirred at 0 & lt; 0 & gt; C overnight.The reaction mixture was filtered.To the filtrate was added isopropanol in a stirred state, the solution was heated to 25 C and stirred for 2.5 hours,To which phosphoric acid is added,Maintaining the temperature below 30 & lt; 0 & gt; C.The mixture was stirred for 30 minutes and the resulting product was filtered, washed with water, and the residue was dried in vacuo to give 2-butyl-4-chloro-1 - ((2 '- (1H-tetrazol- - [1,1'-biphenyl] -4-yl) methyl) -1H-imidazole-5-carboxylic acid.

Reference： [1]Patent: US2008/90885,2008,A1 .Location in patent: Page/Page column 2
[2]Patent: CN104496971,2016,B .Location in patent: Paragraph 0042-0044
[3]Patent: CN104447899,2017,B .Location in patent: Paragraph 0119; 0120; 0121

3
[ 124750-92-1 ]
[ 913611-26-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In acetic acid;	460 grams of free acid was dissolved in 5 liters of acetic acid, glacial. The solution was filtered through a glass frit. The filtrate was added to 6 liters of 1.1 N HCl in acetic acid, glacial over 1 hour. Crystallization began just prior to the end of filtrate addition, and the resulting material was aged for 1 hour. An ice and water bath was added to cool the batch, and the batch was aged 1 hour. 12.5 liters of isopropyl acetate was added over 1 hour, and the resulting material was aged at 3-4C for 1 hour.Resulting material was filtered and washed with 1 liter isopropyl acetate displacement wash, 2 x 1 liter isopropyl acetate slurry wash, and 2.5 liter isopropyl acetate displacement wash. Resulting material was air dried 45 minutes, then dried by pulling nitrogen through filter cake overnight followed by drying at 350C in a vacuum oven until constant weight. The resulting hydrochloric acid salt was 2-butyl~4-chloro- l-[(2'-(l-H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole-5-carboxylic acid hydrochloride Form I. The solid was then analyzed by X-ray Powder Diffraction. The diffractogram for 2-butyl-4-chloro-l-[(2'-(l- H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole-5-carboxylic acid hydrochloride Form I is characterized by principal d-spacings of 12.96, 4.75, 3.97, 3.79, 3.77, 3.71, and 3.44A, more specifically 12.96, 8.32, 8.13, 7.06, 5.18, 4.75, 4.64, 4.45, 4.41, 4.33, 4.19, 3.97, 3.86, 3.79, 3.77, 3.71, 3.59, 3.44, 3.15, and 2.92A.

Reference： [1]Patent: WO2006/115834,2006,A1 .Location in patent: Page/Page column 13

4
[ 124750-99-8 ]
[ 124750-92-1 ]

Yield	Reaction Conditions	Operation in experiment
72%		To a 2000 ml three necked round bottom flask equipped with condenser, mechanical stirrer, and thermometer was added de-ionized water (250 ml), potassium permanganate (0.25 mol) and stirred for about 15 minutes. Tetrabutylammonium chloride (0.30 ml) was added in four portions in 20 minutes. After stirring vigorously for 30 minutes, pyridine (100 ml) and acetone (650 ml) were added and the reaction mixture stirred for another 30 minutes.The dark purple solution was transferred into a 2000 ml three necked flask equipped with condenser, mechanical stirrer, and thermometer. The solution was warmed up to an internal temperature 40 C. Losartan (0.1 ml) [QUESTION: What is the total amount by weight of Losartan?] was added into the reaction mixture in portions with continued stirring. The internal temperature of the reaction mixture was maintained below 50 C. After one hour, the reaction was completed. To the reaction mixture, was added 30% formaldehyde solution (200 ml) slowly with the temperature maintained below 50 C. The reaction mixture was stirred until the purple color disappeared. Brown precipitates were also formed.The contents of the reaction vessel were filtered. The brown solid was washed with 1.0 M NaOH (100 ml×3). The filtrate was almost colorless. The filtrate was concentrated on a rotary evaporator to about of the original volume and stirred with mechanical stirrer and cooled in ice bath. A 6 M HCl solution was added dropwise to reduce the pH of the mixture to about 2. White precipitates were formed during acidification. The precipitate was filtered, washed with de-ionized water, dried in the air and recrystallized in 2-propanol to give white solid of <strong>[124750-99-8]losartan</strong> 5-carboxylic acid (EXP-3174). Yield for the reaction was calculated at 78%.The potassium salt of Losartan was also used for the reaction. The yield was 72%. 1H NMR(DMSO-d6, 400 MHz): 7.64(d, 1H), 6.62(t, 1H), 7.55(t, 1H), 7.59(d, 1H), 7.07(d, 2H), 6.96(d, 2H), 5.62(s, 2H), 2.55(t, 2H), 1.51(q, 2H), 1.21(m, 2H), 0.85(t, 3H)
		To a 22 liter flask equipped with a thermocouple, nitrogen inlet, and mechanical stirrer was added 14 liters of water. To the solution was added 1197 grams (86%) potassium hydroxide pellets and 700 grams <strong>[124750-99-8]<strong>[124750-99-8]losartan</strong> potassium</strong> (2-butyl-4-chloro-l-[p-(o-lH-tetrazol-5-ylphenyl)-benzyl]imidazole-5- methanol), rinsed in with 500 ml water. The resulting solution was cooled to 2C in an isopropanol bath cooled with a chiller unit. Cooling took 2 hours. During this time, a white slurry formed. 775 grams sodium periodate, followed by 16.9 grams ruthenium (UI) chloride hydrate, was added to the slurry, rinsed in with 100 ml water. The temperature rose to 6-6.5C. The resulting slurry was aged at 4-6C. After aging 19 hours, the reaction was complete. After filtering off the solids and washing with 700 ml EPO <DP n="15"/>water, add 130 ml isopropyl alcohol to the filtrate and age 2.5 hours at 18-23 0C. Filter the mixture through a pad of Solka Floe and wash with 600 ml water. The filtrate was acidified with 1.68 L phosphoric acid while maintaining temperature below 31 0C. After aging 30 min, the slurry was filtered and washed with 2 x 4 L water. The dried solids were subsequently decolorized and concentrated resulting in a white slurry that was filtered and washed with 500 ml of cold methanol and air dried.

Reference： [1]Patent: US2008/90885,2008,A1 .Location in patent: Page/Page column 2
[2]Patent: WO2006/115834,2006,A1 .Location in patent: Page/Page column 12-13

Yield	Reaction Conditions	Operation in experiment
89.1%	With potassium permanganate; In water; at -5 - 50℃; for 16h;	4.57 g of 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl) 1,1'-biphenyl-methyl]-5-hydroxymethyl-imidazole was dissolved in 10 ml of water and cooled to -5 C.0 C. The solution of 1.58 g of KMnO4 in 130 ml of water was added dropwise to the resulting solution. After this, the mixture was reacted for 16 hours at 50 C. The reaction was stopped and the reaction mixture was filtered. 50 ml of 1 mol/L NaS2O3 was added to the filtrate. The resulting solution was adjusted to pH 2-3 using diluted hydrochloric acid and went turbid. The solution was extracted with ethyl acetate, dried, concentrated and flash chromatographed using a mixture of petroleum ether and ethyl acetate (1:6 by volume) as the mobile phase, to give 3.85 g of a white solid with a yield of 89.1%.1H-NMR (CDCl3) delta H (ppm): 0.801 (3H, t, J=3.6), 25 (2H, m, J=3.5), 1.49 (2H, m, J=5), 2.56 (2H, t, J=3.5), 5.58 (2H, s), 6.94-7.08 (4H, m, J=5), 7.65-7.50 (2H, m, J=8.5)ESI(-) m/z: 435.1Mp: 125.2-128.5 C.
		Specifically preferred for their antihypertensive activity are: ... 2-Propyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxaldehyde. 2-Butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxaldehyde. 2-(1E-Butenyl)-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-5-hydroxymethyl)imidazole. 2-(1E-Butenyl)-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxaldehyde. 2-Butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]imidazole-5-carboxylic acid. 2-Propyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]imidazole-5-carboxylic acid. 2-Propyl-4-trifluoromethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic acid. 2-Propyl-4-trifluoromethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-5-(hydroxylmethyl)-imidazole. ...
		Most preferred in the method of the invention are compounds of formula II selected from the following, and pharmaceutically acceptable salts thereof. ... 2-Propyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxaldehyde. 2-Butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxaldehyde. 2-(1E-Butenyl)-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-5-hydroxymethyl)imidazole. 2-(1E-Butenyl)-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxaldehyde. 2-Butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl) -biphenyl-4-yl)methyl]imidazole-5-carboxylic acid. 2-Propyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl) -biphenyl-4-yl)methyl]imidazole-5-carboxylic acid. 2-Propyl-4-trifluoromethyl-1-[(2'-(1H -tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic acid. 2-Propyl-4-trifluoromethyl-1-[(2'-(1H -tetrazol-5-yl)biphenyl-4-yl)methyl]-5-(hydroxylmethyl) -imidazole. ...

Specifically preferred for their antihypertensive activity are: ... 2-Propyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxaldehyde. 2-Butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxaldehyde. 2-(1E-Butenyl)-4-chloro-1-[(2'-(1H-tetrazole-5-yl)biphenyl-4-yl)methyl]-5-hydroxymethyl)imidazole. 2-(1E-Butenyl)-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxaldehyde. 2-Butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]imidazole-5-carboxylic acid. 2-Propyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]imidazole-5-carboxylic acid. 2-Propyl-4-trifluoromethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic acid. 2-Propyl-4-trifluoromethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-5-(hydroxylmethyl)-imidazole. ...

6
[ 18274-81-2 ]
[ 538-75-0 ]
[ 124750-92-1 ]
[ 1070174-98-9 ]
[ 2387-23-7 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; In tetrahydrofuran; at 20℃; for 5h;	Step 3:; A solution of dicyclohexylcarbodiimide (DCC) (267.4 mg; 1.3 eq.) in anhydrous THF (10 ml) was added dropwise to a stirred solution of losartan acid (472 mg; 1.08 mmol) prepared as described in step 2, 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (244.5 mg; 1.08 mmol) prepared as above described (step 1) and dimethylaminopyridine (DMAP, 7 mg) in 15 ml of tetrahydrofurane (THF). The reaction is performed at room temperature, stirring under nitrogen for 5 hours. At the end of the reaction the dicyclohexylurea (DCC) is removed by filtration. The solution is evaporated to dryness and the crude product was purified by column chromatography (on silica gel) eluting with CH2C12-methanol (97:3) to give an orange solid with melting point 180-185 C.

Reference： [1]Patent: EP1980559,2008,A1 .Location in patent: Page/Page column 9

7
[ 13700-08-8 ]
[ 538-75-0 ]
[ 124750-92-1 ]
[ 1070174-99-0 ]
[ 2387-23-7 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; In tetrahydrofuran; at 20℃; for 5h;	Step 2:; A solution of dicyclohexylcarbodiimide (DCC) (267.4 mg; 1.3 eq.) in anhydrous THF (10 ml) was added dropwise to a stirred solution of losartan acid (472 mg; 1.08 mmol) prepared as described in EXAMPLE 2, step 2, methanethiosulfonic acid S-(2-hydroxyethyl) ester (1.08 mmol) prepared as above described (step 1) and dimethylaminopyridine (DMAP, 7 mg) in 15 ml of tetrahydrofurane (THF). The reaction is performed at room temperature, stirring under nitrogen for 5 hours. At the end of the reaction the dicyclohexylurea (DCC) is removed by filtration. The solution is evaporated to dryness and the crude product was purified by column chromatography (on silica gel) eluting with CH2Cl2-methanol (98:2) to give the desired product with a melting point of 105-110 C.

Reference： [1]Patent: EP1980559,2008,A1 .Location in patent: Page/Page column 10

8
[ 124750-99-8 ]
[ 124750-92-1 ]

Yield	Reaction Conditions	Operation in experiment
89.1%		4.57g of 2-butyl-4-chloro-1-[2'(1H-tetrazol-5-yl)1,1'-biphenyl-methyl]-5-hydroxymethyl -imidazole was dissolved in 10ml of water and cooled to -5C ? 0C. The solution of 1.58g of KMnO4 in 130ml of water was added dropwise to the resulting solution. After this, the mixture was reacted for 16 hours at 50C. The reaction was stopped and the reaction mixture was filtered. 50ml of 1mol/L NaS2O3 was added to the filtrate. The resulting solution was adjusted to pH 2-3 using diluted hydrochloric acid and went turbid. The solution was extracted with ethyl acetate, dried, concentrated and flash chromatographed using a mixture of petroleum ether and ethyl acetate (1:6 by volume) as the mobile phase, to give 3.85 g of a white solid with a yield of 89.1%. 1H-NMR (CDCl3) delta H (ppm): 0.801(3H, t, J=3.6), 25(2H,m,J=3.5 ),1.49(2H,m,J=5), 2.56(2H,t,J=3.5),5.58(2H,s), 6.94-7.08 (4H,m,J=5),7.65-7.50 (2H,m,J=8.5) ESI(-)m/z: 435.1 Mp: 125.2-128.5C
		Step 2: Preparation of 2-butyl-4-chloro-1-[(2'-(1-H-tetrazol-5-yl)biphenyl-4-yl)methyl]-imidazole-5-carboxylic acid; To a solution of 1.197 g of KOH (86%) in 15 ml of H2O cooled at 2 C, losartan potassium (700 mg), commercially available, was added. After stirring the mixture for 2 hours, sodium periodate (NaIO4, 775 mg) followed by ruthenium (III) chloride hydrate (RuC13.H20, 16.9 mg) was added and the resulting slurry was stirred at 4-6 C for 19 hours under nitrogen. At the end of the reaction, 0.13 ml of isopropyl alcohol were added and the mixture was stirred, at room temperature, for 3 hours. After filtration, 1.68 ml of phosphoric acid were added to the solution and the obtained suspension was stirred for 30 min and then filtered. The residue, washed with water, was dissolved in methanol and decolorized with activated charcoal and finally, after evaporation of the solvent, was washed with ether to yield a white solid with m.p. 176-178 C.
		Water (10 L) was added to a 22 L 4-neck round bottom flask. The water was cooled to 0 0C. At 0 0C, potassium hydroxide (855 g, 15.24 mol) was added followed by losartan potassium (500 g, 1.09 mol)), sodium periodate (554 g, 2.59 mol) and ruthenium (III) chloride hydrate (12 g, 0.05 mol) and the reaction mixture was stirred at 00C overnight. The reaction mixture was filtered. IPA (90 mL) was added to the filtrate while stirring. The solution was warmed to 25 0C and stirred for 2.5 hrs. After 2.5 hrs., phosphoric acid (1200 mL) was added, maintaining the temperature below +30 0C. The mixture was stirred for 30 min and the product was filtered, washing with water. The residue was dried in the vacuum oven at 55 0C overnight. The solid was dissolved in methanol (4 L) and isopropyl acetate (12 L), and charcoal (activated carbon) (100 g) was added. The mixture was stirred at rt for 3.5 hrs, filtered and concentrated. The product was redissolved in DCM/MeOH and precipitated with heptane to afford the title compound as a greenish/brown foam which was used in subsequent steps without further purification.

		Water (10 L) was added to a 22 L 4-neck round-bottom flask. The water was cooled to 0 C. At 0 C, potassium hydroxide (855 g, 15.24 mol) was added, followed by losartan potassium (500 g, 1.09 mol), sodium periodate (554 g, 2.59 mol) and ruthenium (EII) chloride hydrate (12 g, 0.05 mol), and the reaction mixture was stirred at 0 C overnight. The reaction mixture was filtered. Isopropanol (90 mL) was added to the filtrate while stirring. The solution was warmed to 25 C and stirred for 2.5 hours. After 2.5 hours, phosphoric acid (1200 mL) was added, maintaining the temperature below 30 C. The mixture was stirred for 30 minutes and the product was filtered, washing with water. The residue was dried in the vacuum oven at 55 C overnight. The solid was dissolved in methanol (4 L) and isopropyl acetate (12 L), and charcoal (activated carbon) (100 g) was added. The mixture was stirred at room temperature for 3.5 hours, filtered and concentrated. The product was redissolved in dichloromethane/methanol and precipitated with heptane to afford the title compound as a greenish brown foam, which was used in the subsequent step without further purification.
		INTERMEDIATE 11 2-butyl-4-chloro-l-{ [2 '- (2-trityl-2H-tetrazol-5- yl) biphenyl-4-yl ] methyl } -IH-imidazole-5-carboxylic acidStep A: 2-butyl-4-chloro-l- { [2 ' - (lH-tetrazol-5-yl) biphenyl- 4-yl] methyl } -IH-imidazole-5-carboxylic acid; <n="193"/>Water (10 L) was added to a 22 L 4-neck round bottom flask. The water was cooled to 0 0C. At 0 0C, potassium hydroxide (855 g, 15.24 mol) was added followed by losartan potassium (500 g, 1.09 mol)), sodium periodate (554 g, 2.59 mol) and ruthenium (III) chloride hydrate (12 g, 0.05 mol) and the reaction mixture was stirred at 0 0C overnight. The reaction mixture was filtered. IPA (90 mL) was added to the filtrate while stirring. The solution was warmed to 25 0C and stirred for 2.5 hrs . After 2.5 hrs . , phosphoric acid (1200 mL) was added, maintaining the temperature below +30 0C. The mixture was stirred for 30 min and the product was filtered, washing with water. The residue was dried in the vacuum oven at 55 0C overnight. The solid was dissolved in methanol (4 L) and isopropyl acetate (12 L), and charcoal (activated carbon) (100 g) was added. The mixture was stirred at rt for 3.5 hrs, filtered and concentrated. The product was redissolved in DCM/MeOH and precipitated with heptane to afford the title compound as a greenish/brown foam which was used in subsequent steps without further purification.
		Step A: (2-butyl-4-chloro-l- { [2 ' - (lH-tetrazol-5- yl) biphenyl-4-yl ] methyl } -IH-imidazole-5-carboxylic acid (E3174) Water (10 L) was added to a 22 L 4-neck round bottom flask. The water was cooled to 00C. At 00C, potassium hydroxide (855 g, 15.24 mol) was added followed by losartan potassium (500 g, 1.09 mol), sodium periodate(554 g, 2.59 mol) and ruthenium (III) chloride hydrate (12 g, 0.05 mol) and the reaction mixture was stirred at 00C overnight. The reaction mixture was filtered. IPA (90 mL) was added to the filtrate while stirring. The solution was warmed to 25 0C and stirred for 2.5 hrs . After 2.5 hours, phosphoric acid (1200 mL) was added, maintaining the temperature below +300C. The mixture was stirred for 30 min and the product was filtered, washing with water. The residue was dried in the vacuum oven at 55 0C overnight. The solid was dissolved in methanol (4 L) and isopropyl acetate (12 L), and charcoal (activated carbon) (100 g) was added. The mixture was stirred at rt for 3.5 hrs, filtered and concentrated. The product was redissolved in DCM/MeOH and precipitated with heptane to afford the title compound as a greenish/brown foam which was used in subsequent steps without further purification.
		Water (10 L) was added to a 22 L 4-neck round bottom flask. The water was cooled to 0 C. At 0 C, potassium hydroxide (855 g, 15.24 mol) was added followed by losartan potassium (500 g, 1.09 mol)), sodium periodate (554 g, 2.59 mol) and ruthenium (III) chloride hydrate (12 g, 0.05 mol) and the reaction mixture was stirred at 0 C overnight The reaction mixture was filtered. IPA (90 mL) was added to the filtrate while stirring. The solution was warmed to 25 C and stirred for 2.5 hrs. After 2.5 hrs., phosphoric acid (1200 mL) was added, maintaining the temperature below +30 C. The mixture was stirred for 30 min and the product was filtered, washing with water. The residue was dried in the vacuum oven at 55 C overnight. The solid was dissolved in methanol (4 L) and isopropyl acetate (12 L), and charcoal (activated carbon) (100 g) was added. The mixture was stirred at rt for 3.5 hrs, filtered and concentrated. The product was redissolved in DCM/MeOH and precipitated with heptane to afford the title compound as a greenish/brown foam which was used in subsequent steps without further purification.
		Step A: (2-butyl-4-chloro- 1 - { [2'-( 1 H-tetrazol-5-yl)biphenyl-4-yl]methyl} - 1 H-imidazole-5- carboxylic acid (E3174) Water (10 L) was added to a 22 L 4-neck round bottom flask. The water was cooled to 0 0C. At 0 0C, potassium hydroxide (855 g, 15.24 mol) was added followed by losartan potassium (500 g, 1.09 mol)), sodium periodate (554 g, 2.59 mol) and ruthenium (III) chloride hydrate (12 g, 0.05 mol) and the reaction mixture was stirred at 0 0C overnight. The reaction mixture was filtered. IPA (90 mL) was added to the filtrate while stirring. The solution was warmed to 25 C and stirred for 2.5 hrs. After 2.5 hrs., phosphoric acid (1200 mL) was added, maintaining the temperature below +30 C. The mixture was stirred for 30 min and the product was filtered, washing with water. The residue was dried in the vacuum oven at 55 C overnight. The solid was dissolved in methanol (4 L) and isopropyl acetate (12 L), and charcoal (activated carbon) (100 g) was added. The mixture was stirred at rt for 3.5 hrs, filtered and concentrated. The product was redissolved in DCM/MeOH and precipitated with heptane to afford the title compound as a greenish-brown foam which was used in subsequent steps without further purification.

Reference： [1]Patent: EP1988090,2008,A1 .Location in patent: Page/Page column 11
[2]Patent: EP1980559,2008,A1 .Location in patent: Page/Page column 9
[3]Patent: WO2008/76246,2008,A2 .Location in patent: Page/Page column 21
[4]Patent: WO2009/70241,2009,A2 .Location in patent: Page/Page column 20
[5]Patent: WO2009/106471,2009,A2 .Location in patent: Page/Page column 191-192
[6]Patent: WO2009/106470,2009,A2 .Location in patent: Page/Page column 37
[7]Patent: WO2009/140111,2009,A1 .Location in patent: Page/Page column 11; 12
[8]Patent: WO2009/150007,2009,A1 .Location in patent: Page/Page column 67

9
[ 76-83-5 ]
[ 124750-92-1 ]
[ 960231-60-1 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃;	To a solution of E3174 (234.58 g, 0.54 mol) in DCM (4500 niL) was added triethylamine (85 mL, 0.59 mol) followed by a solution of trityl chloride (159 g, 0.56 mol) in DCM (800 mL) and the reaction mixture was stirred at rt overnight. The reaction mixture was washed with water, dried (MgSO4), filtered, and concentrated in vacuo. Chromatography over silica eluting with 20-80% acetone/heptane afforded the title compound as an orange solid.
	With triethylamine; In dichloromethane; at 20℃;	Step B: 2-butyl-4-chloro-l- { [2 ' - (2-trityl-2H-tetrazol-5- yl) biphenyl-4-yl ] methyl } -IH-imidazole-5-carboxylic acid; To a solution of E3174 (234.58 g, 0.54 mol) in DCM (4500 mL) was added triethylamine (85 mL, 0.59 mol) followed by a solution of trityl chloride (159 g, 0.56 mol) in DCM (800 mL) and the reaction mixture was stirred at rt overnight. The reaction mixture was washed with water, dried (MgSO4), filtered, and concentrated in vacuo. Chromatography over silica eluting with 20-80% acetone/heptane afforded the title compound as an orange solid.
	With triethylamine; In dichloromethane; at 20℃;	To a solution of E3174 (234.58 g, 0.54 mol) in DCM (4500 mL) was added triethylamine (85 mL, 0.59 mol) followed by a solution of trityl chloride (159 g, 0.56 mol) in DCM (800 mL) and the reaction mixture was stirred at rt overnight. The reaction mixture was washed with water, dried (MgSO4), filtered, and concentrated in vacuo. Chromatography over silica eluting with 20-80% acetone/heptane afforded the title compound as an orange solid.

Reference： [1]Patent: WO2008/76246,2008,A2 .Location in patent: Page/Page column 21-22
[2]Patent: WO2009/106471,2009,A2 .Location in patent: Page/Page column 192
[3]Patent: WO2009/140111,2009,A1 .Location in patent: Page/Page column 12

10
[ 861405-29-0 ]
[ 124750-92-1 ]
[ 1034453-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 12h;	To a dichloromethane (20 mL) solution of 2-butyl-4-chloro-l-{ [2'-(lH-tetrazol-5-yl)biphenyl-4- yl]methyl}-lH-imidazole-5-carboxylic acid (1.76 g, 3.72 mmol), (2S)-6-hydroxyhexane-l,2-diyl dinitrate (intermediate 3, 0.83 g, 3.72 mmol), l-ethyl-3-(3'-dimethylaminopropyl)carbodiimide hydrochloride (0.85 g, 4.46 mmol), and 1-hydroxybenzotriazole (0.68 g, 4.46 mmol) was added N-methylmorpholine (1.84 mL, 16.7 mmol), followed by MN-dimethylaminopyridine (4.5 mg, 0.04 mmol). After 12 hours, the reaction mixture was washed with saturated sodium bicarbonate solution, brine, dried (magnesium sulfate), filtered, and concentrated in vacuo. Purification of the reaction mixture by reversed-phase mass-directed high-performance liquid chromatography afforded the title compound. 1H nuMR (500 MHz, CD3CN) delta 7.69 (d, J = 7.6 Hz, IH), 7.64 (t, J = 7.6 Hz, IH), 7.53 (t, J = 7.7 Hz, IH), 7.50 (d, J = 7.8 Hz, IH), 7.10 (d, J = 8.2 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 5.63 (s, 2H), 5.34-5.41 (m, IH), 4.83 (dd, J = 2.5, 12.8 Hz, IH), 4.58 (dd, J = 6.2, 13.0 Hz, IH), 4.25 (t, J = 6.2 Hz, 2H), 2.78 (t, J = 7.8 Hz, 2H), 1.79 (q, J = 7.5 Hz, 2H), 1.71 (quintet, J = 6.8 Hz, 2H), 1.48-1.60 (m, 4H), 1.28 (sextet, J = 7.4 Hz, 2H), 0.83 (t, J = 7.3 Hz, 3H); LC-MS: m/z 643 (M + H).

Reference： [1]Patent: WO2008/76246,2008,A2 .Location in patent: Page/Page column 43-44

11
[ 76-83-5 ]
[ 124750-92-1 ]
[ 947331-10-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	To a 100 ml of one-necked flask, 4.36 g of 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)1,1'-biphenyl-methyl]imidazole-5-carboxylic acid, 15 ml of N,N-dimethylformamide, 1.66 g of potassium carbonate and 2.78 g of triphenylchloromethane were added in turn. The mixture was reacted at room temperature overnight. The reaction was stopped and 100 ml of water was added. The resulting mixture was extracted with 100 ml of ethyl acetate and washed once by saturated brine. The organic phase was dried and concentrated to give 7.5g of 2-butyl-4-chlolo-1-[2'-(1-triphenylmethyl-tetrazol-5-yl)1,1'-biphenyl-methyl]-imidazole-5-carboxylic acid as a yellow oil. The crude product obtained from this example was used as material referred to in the following examples without purification.
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	To a 100 ml of one-necked flask, 4.36 g of 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)1,1'-biphenyl-methyl]imidazole-5-carboxylic acid, 15 ml of N,N-dimethylformamide, 1.66 g of potassium carbonate and 2.78 g of triphenylchloromethane were added in turn. The mixture was reacted at room temperature overnight. The reaction was stopped and 100 ml of water was added. The resulting mixture was extracted with 100 ml of ethyl acetate and washed once by saturated brine. The organic phase was dried and concentrated to give 7.5 g of 2-butyl-4-chloro-1-[2'-(1-triphenylmethyl-tetrazol-5-yl) 1,1'-biphenyl-methyl]-imidazole-5-carboxylic acid as a yellow oil. The crude product obtained from this example was used as material referred to in the following examples without purification.
	With triethylamine; In dichloromethane; at 20℃;	To a dichloromethane (4.5 L) solution of 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4- yl]methyl}-1H-imidazole-5-carboxylic acid (235 g, 0.54 mol) was added triethylamine (85 mL,0.59 mol), followed by a dichloromethane (800 mL) solution of trityl chloride (159 g, 0.56 mol), and the reaction mixture was stirred at room temperature overnight. The reaction mixture was washed with water, dried (magnesium sulfate), filtered, and concentrated under reduced pressure.Chromatography over silica eluting with 20-80% acetone/heptane afforded the title compound as an orange solid.

		Example 1 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)1,1'-biphenyl-methyl]imidazole-5-carboxylic acid, 1-[(isopropoxycarbonyl)oxy]methyl ester (compound 1) 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)1,1'-biphenyl-methyl]imidazole-5-carboxylic acid (prepared by the method disclosed in U.S. Pat. No. 5,138,069) was reacted with trityl chloride to obtain 2-butyl-4-chloro-1-[2'-(1-triphenylmethyl-tetrazol-5-yl)1,1'-biphenyl-methyl]imidazole-5-carboxylic acid. To a 100 ml of one-necked flask, 0.523 g of 2-butyl-4-chloro-1-[2'-(1-triphenylmethyl-tetrazol-5-yl)1,1'-biphenyl-methyl]imidazole-5-carboxylic acid, 0.124 g of potassium carbonate, and 5 ml of N,N-dimethylacetamide were added in turn. The solution was stirred at the room temperature for 20 minutes. Then 0.562 g of 1-chloromethyl isopropyl carbonate was added and the mixture was reacted at 45-50 C. for 16 h. After the reaction was completed, the mixture solution was filtered, and 30 ml of water was added into the filtrate. The resulting mixture was extracted with 30 ml of ethyl acetate twice. The organic phase was dried and concentrated to give 1.724 g of oil, which was directly used in the next reaction without purification. 10 ml of dioxane and 5 ml of 4 mol/L HCl were added, and the resulting mixture was reacted at the room temperature for 16 h. After the reaction was completed, the solution was adjusted to pH 6-7 using aqueous sodium bicarbonate solution. The solution became turbid, and was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried, concentrated to give 0.436 g of 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)1,1'-biphenyl-methyl]imidazole-5-carboxylic acid, 1-[(isopropoxycarbonyl)oxy]methyl ester. 1H-NMR: (CDCl3) deltaH (ppm): 0.89 (t, 3H, J=14.6), 1.24 (d, 6H, J=6.3), 1.37 (m, 2H, J=22.1), 1.69 (m, 2H, J=30.5), 2.64 (t, 2H, J=15.5), 4.81 (m, 1H, J=12.4), 5.54 (s, 2H), 5.86 (s, 2H), 6.95-7.64 (8H), 8.08 (d, 1H, J=7.42) ESI (+) m/z: 552.7
	With triethylamine; In dichloromethane; at 20℃;	Step B: To a solution of the product of step A in dichloromethane was added triethylamine, Followed by the addition of triphenylmethyl chloride in methylene chloride, And the resulting reaction mixture was stirred at room temperature. Washing the reaction mixture with water, Magnesium sulfate, Filtered, concentrated in vacuo, loaded on a silica gel column eluting with 20-80% acetone / n-hexane to give 2-butyl-4-chloro-1- [2 '- (2-trityl- 2H-tetrazolidine-5) biphenyl-4-ylmethyl} -1H-imidazole-5-carboxylic acid.
	With triethylamine; In dichloromethane; at 20℃;	Step B: To the dichloromethane solution of step A product was added triethylamine followed by the addition of triphenylmethyl chloride in methylene chloride and the resulting reaction mixture was stirred at room temperature. The reaction mixture was triturated with water, dried over magnesium sulfate, filtered, concentrated in vacuo, loaded on a silica gel column and eluted with 20-80% acetone / n-hexane to give2-Butyl-4-chloro-1 - [2 '- (2-trityl-2H-tetrazolyl-5) biphenyl-4-] methyl} -1H-imidazole- carboxylic acid.
	With triethylamine; In dichloromethane; at 20℃;	Step B: 2-butyl-4-chloro-l- { [2 ' - (2-trityl-2H-tetrazol-5- yl) biphenyl-4-yl] methyl } -IH-imidazole-5-carboxylic acid <n="40"/> To a solution of E3174 (234.58 g, 0.54 mol) in DCM (4500 mL) was added triethylamine (85 mL, 0.59 mol) followed by a solution of trityl chloride (159 g, 0.56 mol) in DCM (800 mL) and the reaction mixture was stirred at rt overnight. The reaction mixture was washed with water, dried (MgSO4), filtered, and concentrated in vacuo. Chromatography over silica eluting with 20-80% acetone/heptane afforded the title compound as an orange solid.
	With triethylamine; In dichloromethane; at 20℃;	Step B: 2-butyl-4-chloro-l-[2'-(2-trityl-2H-tetrazol-5-yl)biphenyl-4-yl]methyl}-lH-imidazole-5- carboxylic acid To a solution of E3174 (234.58 g, 0.54 mol) in DCM (4500 niL) was added triethylamine (85 niL, 0.59 mol) followed by a solution of trityl chloride (159 g, 0.56 mol) in DCM (800 mL) and the reaction mixture was stirred at rt overnight. The reaction mixture was washed with water, dried (MgSO4), filtered, and concentrated under reduced pressure. Chromatography over silica gel eluting with acetone/heptane 20:80% afforded the title compound as an orange solid.

Reference： [1]Patent: EP1988090,2008,A1 .Location in patent: Page/Page column 11
[2]Patent: US2009/36505,2009,A1 .Location in patent: Page/Page column 8-9
[3]Patent: WO2009/70241,2009,A2 .Location in patent: Page/Page column 20
[4]Patent: US2009/326024,2009,A1 .Location in patent: Page/Page column 4
[5]Patent: CN104496971,2016,B .Location in patent: Paragraph 0042; 0043; 0045
[6]Patent: CN104447899,2017,B .Location in patent: Paragraph 0119; 0120; 0122
[7]Patent: WO2009/106470,2009,A2 .Location in patent: Page/Page column 37-38
[8]Patent: WO2009/150007,2009,A1 .Location in patent: Page/Page column 67-68

12
[ 35180-01-9 ]
[ 124750-92-1 ]
[ 947331-05-7 ]

Yield	Reaction Conditions	Operation in experiment
		To a 100 ml of one-necked flask, 0.523g of 2-butyl-4-chloro-1-[2'-(1-tri-benzyl-tetrazol-5-yl)1,1'-biphenyl-methyl] imidazole-5-carboxylic acid, 0.124g of potassium carbonate, 5 ml of N,N-dimethylacetamide were added in turn. The solution was stirred at room temperature for 20 minutes. Then 0.562g of 1-chloromethyl isopropyl carbonate was added and the mixture was reacted at 45-50C for 16 hours. After the reaction was completed, the mixture solution was filtered, and 30ml of water was added into the filtrate. The resulting mixture was extracted with 30ml of ethyl acetate twice. The organic phase was dried and concentrated to give 1.724g of oil, which was directly used in the next reaction without purification. 10ml of dioxane and 5ml of 4 mol/L HCl were added, and the resulting mixture was reacted at room temperature for 16 hours. The reaction was stopped and the solution was adjusted to pH 6-7 using aqueous sodium bicarbonate solution. The solution went turbid, and was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried, concentrated to give 0.436g of 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)1,1'-biphenyl-methyl] imidazole-5-carboxylic acid, 1-[(isopropoxy)carbonyloxy] methyl ester. The structure's spectrum data of the compound is as below: 1H-NMR (CDCl3) delta H (ppm): 0.89(t,3H,J=14.6),1.24(d,6H,J=6.3), 1.37(m,2H,J=22.1), 1.69(m,2H,J=30.5),2.64(t,2H,J=15.5),4.81(m,1H,J=12,4),5.54(s,2H),5.86(s,2H), 6.95-7.64(8H),8.08(d,1H,J=7.42) ESI()m/z:552.7 Mp:134.5-136C

Reference： [1]Patent: EP2116242,2009,A1 .Location in patent: Page/Page column 9

13
(3S,3aR,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl [(3H-fluoren-9-ylmethoxy)carbonyl]amino}acetate [ No CAS ]
[ 124750-92-1 ]
[ 1185768-61-9 ]

Yield	Reaction Conditions	Operation in experiment
		Step B: (3S, 3a.R, 6R, 6aS) -6- (nitrooxy) hexahydrofuro [3, 2- b] furan-3-yl { [ (2-butyl-4-chloro-l- { [2 '- (ltf-tetrazol-5- yl) biphenyl-4-yl] methyl } -lff-imidazol-5-yl) carbonyl] amino } acetate; To a N, N-dimethylformamide solution (100 mL) of(35, 3a.R, 6R16aS) -6- (nitrooxy) hexahydrofuro [3, 2-b] furan-3-yl{ [( 9H-fluoren-9-ylmethoxy) carbonyl] amino } acetate (8.33 g,17.7 mmol) was added piperidine (1.75 mL, 17.7 mmol) .After 1 hour, 2-butyl-4-chloro-l- { [2 ' - (lH-tetrazol-5- yl) biphenyl-4-yl] methyl } -lH-imidazole-5-carboxylic acid (3.18 g, 7.27 mmol), (benzotriazol-1- yloxy) tripyrrolidinophosphonium hexafluorophosphate (4.06 g, 7.79 mmol) and triethylamine (4.0 mL, 28.7 mmol) were added, and the reaction mixture was stirred overnight. Purification of the reaction mixture by reversed-phase mass-directed high-performance liquid chromatography afforded the title compound.1H-NMR (CDCl3) : 7.77 (IH, d, J = 7.6Hz); 7.57 (IH, t, J = 1.7Hz) ; 7.44-7.52 (2H, m) ; 7.40 (IH, d, J = 7.6Hz); 7.01 (2H, d, J = 8.0Hz); 6.94 (2H, , J = 8.0Hz); 5.50 (2H, s); 5.33 (IH, dt, J = 2.6, 5.4Hz); 5.20 (IH, d, J = 2.8Hz); 4.96 (IH, t, J = 5.2Hz); 4.48 (IH, , J = 4.8Hz); 4.11 (2H, d, J = 5.2Hz); 3.98 (IH, t, J = 10.9Hz); 3.91-3.97 (2H, m) ; 3.84 (IH, dd, J = 5.4, 11.3Hz); 2.78 (2H, t, J = 7.8Hz); 1.61 (2H, quintet, J = 7.7Hz), 1.32 (2H, sextet, J = 7.5Hz) , 0.84 (3H, t, J = 7.4Hz) . LC-MS: m/z 667 (M + H) .

Reference： [1]Patent: WO2009/106471,2009,A2 .Location in patent: Page/Page column 183

14
[ 16106-20-0 ]
[ 124750-92-1 ]
[ 1196117-80-2 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;dmap; In dichloromethane; for 48h;	A m ixture of 2-buty I-4-ch loro- 1 - { [2'-( 1 H-tetrazol-5-yl)bipheny l-4-yl]methy 1 } - 1 H-imidazo.e-5 -carboxy I ic acid (Step A, Intermediate 4, 7.83 g, 16.5 mmol), isosorbide-5-mononitrate (1.55 g, 8.11 mmol), l-ethyl- 3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.78 g, 19.7 mmol), 1-hydroxybenzotriazole (1.25 g, 8.16 mmol), 4-dimethylaminopyridine (0.10 g, 0.82 mmol), and N-methylmorpholine (9.0 mL, 82 mmol) was dissolved in dichloromethane (150 mL) and stirred for 2 days. It was then concentrated in vacuo and purified by reversed-phase mass-directed etaPLC (Sunfire C-18) to afford the title compound. 1H NMR (500 MHz, CDCl3) delta 8.02 (dd, J = 7.6, 1.0 Hz, 1H), 7.61 (td, 7= 7.6, 1.3 Hz, 1H), 7.55 (td, J= 7.7, 1.1 Hz, 1H), 7.43 (d, J= 7.8 Hz, 1H), 7.18 (d, J= 7.7 Hz, 2H), 6.96 (d, J= 7.8 Hz, 2H), 5.5O (s, 2H), 5.40 (td, J= 5.4, 3.0 Hz, 1H), 5.32-5.30 (m, 1H), 4.99 (t, J= 5.2 Hz, 1H), 4.51 (d, J= 5.0 Hz, 1H), 4.06- <n="20"/>4.02 (m, 3H), 3.99 (dd, J= 1 1.4, 5.4 Hz, 1H), 2.68 (t, J= 7.7 Hz, 2H), 1.69 (quintet, J= 7.7 Hz, 2H), 1.36 (sextet, J= 7.5 Hz, 2H), 0.89 (t, J= 7.3 Hz, 3H); LC-MS: m/z 610.1 (M + H).

Reference： [1]Patent: WO2009/140111,2009,A1 .Location in patent: Page/Page column 17; 18

15
[ 114798-36-6 ]
[ 124750-92-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium permanganate; potassium hydroxide; In water; N,N-dimethyl-formamide; at 20 - 30℃; for 2h;Large scale;	385g of potassium permanganate and 130g of potassium hydroxide were dissolved in 1250g of water. 1500g of water and 750g DMF mixed solvent were used to dissolve 275g 5-aldehyde losartan. this was added dropwise with stirring to the aqueous solution of alkaline potassium permanganate. Temperature was not to exceed 30C. After the dropwise addition, it was stirred for 2 hours at room temperature. After completion of the reaction, 20% sodium sulfite solution was added to the system until purple color faded. Temperature was not to exceed 30C. The solid was removed by filtration (Celite filter aid) and was added water then extracted with ethyl acetate (1250mL × 2). The organic phase was discarded and the aqueous phase retained. With 10% dilute hydrochloric acid, the aqueous phase was adjusted to pH 4.5. it was filtered and the filter cake was washed with water (500 mL). After drying under vacuum, it gave a crude product 873g, yield 95%.

Reference： [1]Patent: CN105218527,2016,A .Location in patent: Paragraph 0016

16
[ 124750-92-1 ]
(3aS,6aR)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl((1-((2'-(1H-tetrazole-5yl)[1,1'-biphenyl]-4-yl)methyl)2-butyl-4-chloro-1H-imidazol-5-yl)formyl)-L-alanyl-L-proline [ No CAS ]

Reference： [1]Patent: CN104496971,2016,B

17
[ 124750-92-1 ]
2-butyl-4-chloro-1-((2'-(1-trityl-1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylic acid chloride [ No CAS ]

Reference： [1]Patent: CN104496971,2016,B
[2]Patent: CN104447899,2017,B

18
[ 124750-92-1 ]
((1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-butyl-4-chloro-1H-imidazol-5-yl)carbonyl)-L-alanyl-L-proline-(3aS,6aR)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl ester [ No CAS ]

Reference： [1]Patent: CN104447899,2017,B

19
[ 124750-92-1 ]
[ 913611-27-5 ]

Reference： [1]Patent: WO2006/115834,2006,A1

20
[ 124750-92-1 ]
[ 1185769-65-6 ]

Reference： [1]Patent: WO2009/106471,2009,A2

21
[ 124750-92-1 ]
[ 1185769-66-7 ]

Reference： [1]Patent: WO2009/106471,2009,A2

22
[ 124750-92-1 ]
[ 1185768-56-2 ]

Reference： [1]Patent: WO2009/106471,2009,A2

23
[ 124750-92-1 ]
[ 1186123-58-9 ]

Reference： [1]Patent: WO2009/106470,2009,A2

24
[ 124750-92-1 ]
[ 1186124-18-4 ]

Reference： [1]Patent: WO2009/106470,2009,A2

25
[ 124750-92-1 ]
[ 1200445-28-8 ]

Reference： [1]Patent: WO2009/150007,2009,A1

26
[ 124750-92-1 ]
[ 1200445-39-1 ]

Reference： [1]Patent: WO2009/150007,2009,A1

27
[ 136540-89-1 ]
[ 124750-92-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrabutylammomium bromide; sodium hydroxide / toluene / 20 h / 60 °C 2: sodium azide; trimethylamine hydrochloride / toluene; 1-methyl-pyrrolidin-2-one / 43 h / 60 °C 3: sodium hydroxide / ethanol / 20 h / 90 °C

Reference： [1]Current Patent Assignee: DAEJEON UNIVERSITY - KR2020/82424, 2020, A

28
[ 114772-54-2 ]
[ 124750-92-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrabutylammomium bromide; sodium hydroxide / toluene / 20 h / 60 °C 2: sodium azide; trimethylamine hydrochloride / toluene; 1-methyl-pyrrolidin-2-one / 43 h / 60 °C 3: sodium hydroxide / ethanol / 20 h / 90 °C

Reference： [1]Current Patent Assignee: DAEJEON UNIVERSITY - KR2020/82424, 2020, A

29
[ 947330-97-4 ]
[ 124750-92-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydroxide In ethanol at 90℃; for 20h;	1.c (c) Preparation of losartan metabolite EXP-3174 Ethyl 1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-butyl-4-chloro- obtained from (b) above 1H-imidazole-5-carboxylate 40 mg (Chemical Formula 4-1, 0.086 mmol) was dissolved in 0.6 mL of ethanol, and 0.14 mL (0.26 mmol) of 2 N NaOH was added, followed by heating at 90 °C to reflux.After 20 hours, when the reaction was completed, the reaction vessel was cooled to room temperature.After cooling the reaction vessel to 0° C. again, 1 N HCl was added dropwise until the pH of the solution became 3-4, and extracted twice with 15 ml of EtOAc.The extracted organic layer was dried over anhydrous MgSO4, filtered and concentrated. The concentrated crude product was purified by flash column chromatography (EtOAc: MeOH = 2: 1) and concentrated to obtain a losartan metabolite EXP-3174 (white solid). % Yield.

Reference： [1]Current Patent Assignee: DAEJEON UNIVERSITY - KR2020/82424, 2020, A Location in patent: Paragraph 0073-0075; 0082-0084

30
[ 124750-92-1 ]
[ 149709-62-6 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
3.5 g	With calcium hydroxide In lithium hydroxide monohydrate; propan-2-one at 20℃; for 18h; Inert atmosphere;	2-3 Preparation of complex: (prepared according to Example 2 of patent WO2017125031A1) At room temperature, add AHU377 free acid 2.36g, EXP3174 2g and 40mL acetone obtained according to the method of Example 1 into a 250mL there-necked flask, and dissolve it; at room temperature, add calcium hydroxide solid and 1mL water relative to AHU377 1.3 equivalents, stir at room temperature 10h, add 40mL of acetone, react for 8h, filter through a Buchner funnel under nitrogen protection, rinse the solid with acetone to obtain a white solid, vacuum dry at 35°C for 8h, and dry to obtain 3.5g of solid (EXP3174·AHU377) 3 -·1.5Ca 2+·2.5H 2O, 99% pure by HPLC.
3.5 g	With calcium hydroxide In lithium hydroxide monohydrate; propan-2-one at 20℃; for 18h; Inert atmosphere;	2-3 Preparation of the complex: (prepared in accordance with Example 2 of Patent WO2017125031A1) At room temperature, the AHU377 free acid 2.36g, EXP3174 2g and 40mL acetone obtained according to Example 1 method was added to a 250mL three-mouth bottle, dissolved; at room temperature, added relative to AHU377 1.3 equivalent calcium hydroxide solids and 1mL of water, stirred at room temperature for 10h, supplemented with 40mL acetone, and then reacted for 8h, nitrogen protection by Brinell funnel extraction, the solid was washed with acetone, to obtain a white solid, vacuum baked at 35 ° C for 8h, dried to obtain a solid 3.5g ( EXP3174· AHU377)3-·1.5Ca2+·2.5H2O, HPLC test purity of 99%. Repeat the test to obtain an adequate dose of pharmacodynamic experiments.

Reference： [1]Current Patent Assignee: SHENZHEN SALUBRIS PHARMACEUTICALS CO., LTD. - WO2021/254409, 2021, A1 Location in patent: Page/Page column 5-6
[2]Current Patent Assignee: SHENZHEN SALUBRIS PHARM CO LTD; SHENZHEN SALUBRIS PHARMACEUTICALS CO., LTD. - WO2022/37512, 2022, A1 Location in patent: Page/Page column 4-6

31
[ 124750-92-1 ]
[ 2782690-89-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere 2: Sodium hydrogenocarbonate; tetrabutylammonium hydrogensulfate / lithium hydroxide monohydrate; dichloromethane / 7 h / 0 - 25 °C

Reference： [1]Current Patent Assignee: ACHE LABORATORIOS FARMACEUTICOS SA - WO2022/120442, 2022, A1

32
[ 124750-92-1 ]
[ 2782690-90-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere 2: Sodium hydrogenocarbonate; tetrabutylammonium hydrogensulfate / lithium hydroxide monohydrate; dichloromethane / 7 h / 0 - 25 °C 3: Cs₂CO₃ / N,N-dimethyl-formamide / 5 h / 20 °C

Reference： [1]Current Patent Assignee: ACHE LABORATORIOS FARMACEUTICOS SA - WO2022/120442, 2022, A1

33
[ 124750-92-1 ]
[ 2782690-91-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere 2: sodium hydrogencarbonate; tetra(n-butyl)ammonium hydrogensulfate / water; dichloromethane / 7 h / 0 - 25 °C 3: caesium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 4: 10% Pd/C; hydrogen; lithium chloride / tetrahydrofuran; ethanol / 10 h / 25 °C

Reference： [1]Current Patent Assignee: ACHE LABORATORIOS FARMACEUTICOS SA - WO2022/120442, 2022, A1

34
[ 124750-92-1 ]
[ 2782690-92-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: triethylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; tetra(n-butyl)ammonium hydrogensulfate / water; dichloromethane / 7 h / 0 - 25 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 5 h / 20 °C 4.1: 10% Pd/C; hydrogen; lithium chloride / tetrahydrofuran; ethanol / 10 h / 25 °C 5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 18 °C 5.2: 1 h

Reference： [1]Current Patent Assignee: ACHE LABORATORIOS FARMACEUTICOS SA - WO2022/120442, 2022, A1

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Imidazoles

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 124750-92-1 ] {[proInfo.proName]}

Quality Control of [ 124750-92-1 ]

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[ 124750-92-1 ] Synthesis Path-Downstream 1~34

Related Functional Groups of [ 124750-92-1 ]

Aryls

Chlorides

Esters

Carboxylic Acids

Related Parent Nucleus of [ 124750-92-1 ]

Imidazoles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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[ 124750-92-1 ]

Related Parent Nucleus of
[ 124750-92-1 ]