[ CAS No. 103577-45-3 ] {[proInfo.proName]}

Name: 103577-45-3|2-(((3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazole|98%
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SKU: A281446
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Quality Control of [ 103577-45-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 103577-45-3 ]

SDS Specification

Alternatived Products of [ 103577-45-3 ]

Product Details of [ 103577-45-3 ]

CAS No. :	103577-45-3	MDL No. :	MFCD00866873
Formula :	C₁₆H₁₄F₃N₃O₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MJIHNNLFOKEZEW-UHFFFAOYSA-N
M.W :	369.36	Pubchem ID :	3883
Synonyms :	AG-1749;A-65006;Lansoprazole, AG-1749, Prevacid, Zoton, Agopton, Bamalite, Opiren	Chemical Name :	2-(((3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazole

Calculated chemistry of [ 103577-45-3 ]

Physicochemical Properties

Num. heavy atoms :	25
Num. arom. heavy atoms :	15
Fraction Csp3 :	0.25
Num. rotatable bonds :	6
Num. H-bond acceptors :	7.0
Num. H-bond donors :	1.0
Molar Refractivity :	87.24
TPSA :	87.08 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.42 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.2
Log Po/w (XLOGP3) :	3.01
Log Po/w (WLOGP) :	5.49
Log Po/w (MLOGP) :	1.57
Log Po/w (SILICOS-IT) :	3.54
Consensus Log Po/w :	3.16

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-4.07
Solubility :	0.0311 mg/ml ; 0.0000843 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.5
Solubility :	0.0116 mg/ml ; 0.0000314 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-6.84
Solubility :	0.0000529 mg/ml ; 0.000000143 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.4

Safety of [ 103577-45-3 ]

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 [ 103577-45-3 ]

* 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 [ 103577-45-3 ]

[ 103577-45-3 ] Synthesis Path-Downstream 1~12

1
[ 103577-66-8 ]
[ 103577-45-3 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1990,vol. 38,p. 2853 - 2858
[2]Patent: CN107011252,2017,A

2
[ 1288338-69-1 ]
[ 103577-45-3 ]

Yield	Reaction Conditions	Operation in experiment
	With urea hydrogen peroxide addition compound In 1-methyl-pyrrolidin-2-one at 0 - 20℃;	2.b 20 g (0.0538 mole) of 2-[[[3-methyl-4-(2,2,2-trifluoro-ethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole hydrate were dissolved in 60 ml of 1-methyl-2-pyrrolidone (NMP) at room temperature, then 0.080 g (0.6 mmole) vanadium(V) oxytrifluoride were added and the reaction mixture was cooled to a temperature of from 0 to 5°C. 8.1 g (0.0861 mole) of hydrogen peroxide urea adduct were suspended (optionally per partes) and the reaction was carried out at a temperature of from 0 to 10°C for half an hour then at a temperature of from 10 to 15°C until the reaction was completed. At the end of the reaction 0.5 ml of triethylamine and a solution of 11.36 g sodium thiosulphate pentahydrate in 12 ml of water were added. The product was precipitated with water (120 ml at 20 +/- 5°C) and filtered off to obtain 16.8 g of wet lansoprazole
16.2 kg	With dihydrogen peroxide; vanadium pentoxide In ethanol at 16 - 65℃; Large scale;	1.2; 1.3; 2.2; 2.3; 3.2; 3.3; 4.2; 4.3 step (2) The preparation of lansoprazole crude product The preparation of step (2) lansoprazole crude productThe solid dry matter lansoprazole sulfide and vanadium pentoxide are added to the ethanol solvent, and after the reaction is stirred for 20-30 min at a temperature of 50 ° C, the temperature is lowered to below 25 ° C, and hydrogen peroxide with a concentration of 30% is added, and at 40 ° C. After stirring the reaction for 1.5°C, TLC monitored the reaction end point, cooled to 0°C, crystallized, and centrifuged to dry to obtain crude lansoprazole;Specific operation process The preparation and preparation of the solution:Preparation of sodium thiosulfate solution: 1.6 kg of sodium thiosulfate was added to 4.9 kg of purified water, and stirred to dissolve for later use.Preparation of sodium carbonate solution: take 55.0 g of anhydrous sodium carbonate, add it to 147.0 kg of purified water, and stir to dissolve for later use. Preparation of cold ethanol: Weigh 6.1 kg of ethanol and cool it to below 10°C for later use.Oxidation reaction:300L stainless steel reactor under stirring (rotation controller reading is 12.0-16.0Hz, corresponding rotating speed 48-64r/min.) Add ethanol 97.65kg, lansoprazole sulfide (intermediate I) 21.7kg, vanadium pentoxide 217.0g.After feeding, heat to 30-65°C, keep warm, and stir (the reading of the speed controller is 12.0-16.0Hz, corresponding to the speed of 48-64r/min.) for 20-30min.The system was cooled to below 25°C, and 6.51 kg of 30% hydrogen peroxide was slowly added.After the addition of materials, the temperature is controlled at 16-55°C and the reaction is stirred for about 1-3h.(After 1.5 hours of reaction, samples were taken every 10-15 minutes, and the reaction was monitored by TLC.)Note: With the progress of the reaction, a large amount of products are precipitated and attached to the wall of the kettle, which affects the heat transfer.At this time, it is necessary to stop stirring, and use a steel shovel to disperse the product adhering to the kettle wall in the kettle and continue the reaction.Monitoring of the reaction end point: take about 0.25 ml of the reaction solution, add an appropriate amount of ethyl acetate to dilute to about 1.0 ml, shake well, and use it as the test solution; take about 30 mg of lansoprazole sulfide, add about 10 ml of ethyl acetate to make the solution. dissolved as a control solution.Draw 2-5ul of each of the above two solutions, respectively, point them on the same silica gel GF254 thin-layer plate, use petroleum ether (60-90):ethyl acetate (1:2) as the developing agent, develop, and place the ultraviolet light Viewed under light (254nm).The size and brightness of the lansoprazole sulfide spot in the chromatogram of the test product are not greater than that of the lansoprazole sulfide spot in the control solution, and the reaction end point is reached.Post-processing:Stirring speed: the reading of the speed controller is 12.0-16.0Hz, corresponding to the speed of 48-64r/min.Add 6.5kg of sodium thiosulfate solution to the above reaction system under stirring, cool down to 0-5°C, keep stirring for 1 hour for crystallization, under stirring, slowly discharge material into the centrifuge (the working mode of the centrifuge is high speed), put After the material is finished, centrifuge (the centrifuge working mode is high speed) for 10-15min.Rinse the filter cake with 6.1kg of cold ethanol and centrifuge (centrifuge working mode is high speed) for about 10-15min.The full amount of sodium carbonate solution was added to the 300L reaction kettle, and then the filter cake was transferred to the kettle for stirring and dispersion for 10-15min.In the stirring state, slowly discharge the material into the centrifuge for centrifugation (the working mode of the centrifuge is high speed), and continue to centrifuge (the working mode of the centrifuge is high speed) after the discharge is completed for 1-1.5h to obtain the wet weight of the crude lansoprazole product. About 31.6kg (after deducting the loss on drying, the crude lansoprazole is converted to about 21.6kg).The preparation of step (3) lansoprazole fine product The crude lansoprazole was added to the mixture of ethanol, acetone, disodium EDTA, purified water and ammonia water, wherein vacuum crystallization was performed at 30°C, centrifugal filtration, washing and drying were performed to obtain lansoprazole Excellent product; the density of ethanol is 0.81g/ml; the density of acetone is 0.79g/ml; the density of ammonia water is 0.91g/ml; the molar ratio of the added amount of disodium EDTA to the catalyst vanadium pentoxide is 1:1.The specific process is:The preparation of the solution:The preparation of the mixed solution: 2.6 kg of ethanol, 3.8 kg of acetone, and 1.6 kg of purified water are mixed, stirred evenly, and cooled to below 10° C. for later use.Preparation of sodium carbonate solution: add 37.0 g of anhydrous sodium carbonate, add 100.0 kg of purified water, and stir to dissolve for later use.Dissolve:Stirring speed: the reading of the speed controller is 20.0-25.0Hz, corresponding to the speed of 80-100r/min.64.8kg of ethanol, 94.6kg of acetone, 28.4kg of purified water (40kg minus 11.6kg of wet product moisture content) and 444.0g of disodium EDTA were added to the 300L stainless steel reaction kettle under stirring.Replace the air in the kettle with nitrogen once (cover the feeding port, open the vacuum valve, draw out the air in the kettle until the vacuum gauge shows 0.04-0.06MPa, close the vacuum valve, open the nitrogen valve and let in nitrogen until the reading of the vacuum gauge returns to zero).20.0 kg of lansoprazole crude product was added under the condition of nitrogen positive pressure, and the air in the kettle was replaced 3 times according to the above-mentioned operation mode.Put 2.96kg of ammonia water in the stainless steel feeding tank and add it into the reaction kettle, heat up to 30°C and stir until it is dissolved, and after the solution is clear, control the temperature (15-38°C) and continue to stir for 15-20min. Filtration and crystallization:Replace the 300L reaction kettle with nitrogen once (open the vacuum valve of the crystallization kettle, draw out the air in the kettle, until the vacuum gauge shows 0.06-0.08MPa, close the vacuum valve of the crystallization kettle, open the nitrogen valve and let in nitrogen until the reading of the vacuum gauge returns to zero), gas After the replacement is complete,Online filtration (the filter housing is stainless steel, the filter element material is PTFE, the pore size is 0.22um, and it is disposable), and the filtrate is pumped under stirring (the reading of the speed controller is 20.0-25.0Hz, and the corresponding speed is 80-100r/min.) ) in a 300L reaction kettle, cooled to 0 °C, and stirred for crystallization for 2 h under nitrogen protection. Centrifugation and post-processing: (this process uses two centrifuges to process at the same time)Stirring speed: The reading of the revolution controller is 20.0-25.0Hz, and the corresponding rotation speed is 80-100r/min.After the crystallization is completed, in a stirring state, slowly discharge the material to the two open centrifuges for centrifugation (the rotation speed is greater than 1500r/min).The filter cakes were rinsed with 2.0kg of mixed solution below 10°C in the centrifugal state respectively. After feeding, continue centrifugation (rotation speed greater than 1500r/min) for 10-15min to collect the filter cakes.60.0kg of sodium carbonate solution was added into the cleaned 300L reaction kettle, and the filter cake was transferred to the kettle for stirring and dispersing for 10-15min.In the stirring state, slowly discharge the material to the two open centrifuges for centrifugation (the speed is greater than 1500r/min).The filter cake is first rinsed with 20.0kg of sodium carbonate solution under centrifugal state, and then rinsed with 2.0kg of mixed solution. After feeding, continue to be centrifuged (the rotation speed is greater than 1500r/min) for 1-1.5 hours.The filter cake is collected and dispersed into a drying bag.Baking material:Dry under reduced pressure at 30-35°C (vacuum display 0.08--0.1MPa) for 3 hours, then heat up to 40-45°C under reduced pressure (vacuum display 0.08-0.1MPa) and dry, turn the material every 3 hours, and bake until moisture Below 0.5% (measured with a quick moisture meter).About 16.2kg of lansoprazole finished product is obtained by receiving the materials.

Reference： [1]Current Patent Assignee: KRKA DD NOVO MESTO - EP1681056, 2006, A1 Location in patent: Page/Page column 9
[2]Current Patent Assignee: SICHUAN ZIREN PHARMACEUTICAL - CN113773301, 2021, A Location in patent: Paragraph 0028; 0042-0074; 0086-0118; 0130-0162; 0175-0206

3
[ 1116-76-3 ]
[ 408332-88-7 ]
[ 103577-40-8 ]
[ 103577-45-3 ]

Yield	Reaction Conditions	Operation in experiment
	With isopropylbenzene hydroperoxide;titanium(IV) isopropylate; In water; toluene;	Example 17 Production of (R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole Under a nitrogen atmosphere, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]thio]benzimidazole (5.00 g, 0.014 mol), toluene (35 mL), water (28 mg, 0.0016 mol, total water content 0.0017 mol) and diethyl (+)-tartrate (1.33 mL, 0.0078 mol) were mixed, and the mixture was stirred at 50 to 55 C. for 30 min. Under a nitrogen atmosphere, titanium(IV) isopropoxide (1.04 mL, 0.0035 mol) was added to the mixture, and the mixture was stirred at 50 to 55 C. for 1 hr. Under a nitrogen atmosphere and under cooling, to the obtained mixture was added <strong>[1116-76-3]trioctylamine</strong> (2.04 mL, 0.0047 mol) and then cumene hydroperoxide (3.78 mL, 0.021 mol) was added at 15 to 20 C. The mixture was reacted by stirring at 15 to 20 C. for 1.5 hr. The reaction mixture was analyzed by high performance liquid chromatography (conditions (A)). As a result, it was found that 5.4% of a sulfide form and 5.4% of a sulfone form were present as analogous substances in the reaction mixture, and other analogous substances were not present. The enantiomer excess of the title compound in the reaction mixture was 98.1% ee.

Reference： [1]Patent: US2003/171591,2003,A1

4
[ 788133-24-4 ]
[ 1288338-69-1 ]
[ CAS Unavailable ]
[ 103577-45-3 ]

Yield	Reaction Conditions	Operation in experiment
89.5%	With dihydrogen peroxide; sodium thiosulfate In ethanol	3 EXAMPLE 3 EXAMPLE 3 2-[[3-Methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylthio]benzimidazole (monohydrate) (20.0 g) was dissolved in ethanol (150 ml), to which was added dropwise at about 20° C. a solution of vanadium pentaoxide (30 mg) in a mixture of 35% aqueous solution of hydrogen peroxide (6.14 g) and ethanol (6 ml), and allowed to react at 18°-22° for about 2.5 hours. After completion of the reaction an aqueous solution of sodium thiosulfate (2 g/60 ml) was added to the reaction mixture, which was stirred by ice-cooling for about 1 hour. The crystals were collected by filtration and washed with an ice-cooled mixture of ethanol-water (1:1). The crystals thus obtained were treated with a mixture of ethanol-water (9:1, 100 ml), heated (70°-80° C.) and stirred so that the crystals were dissolved, then the insoluble matters were removed by hot filtration. The filtrate was ice-cooled for crystallization, and the crystals were collected by filtration, washed with ice-cooled ethanol-water mixture (8:2) and dried in vacuo, to give white needles of 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylsulfinyl]benzimidazole (17.8 g). (yield: 89.5%). m.p. 177°-178° C. (decomposed)
89.5%	With dihydrogen peroxide; sodium thiosulfate In ethanol	3 Example 3 Example 3 2-[[3-Methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylthio]benzimidazole (monohydrate) (20.0 g) was dissolved in ethanol (150 ml), to which was added dropwise at about 20°C a solution of vanadium pentaoxide (30 mg) in a mixture of 35% aqueous solution of hydrogen peroxide (6.14 g) and ethanol (6 ml), and allowed to react at 18-22° for about 2.5 hours. After completion of the reaction an aqueous solution of sodium thiosulfate (2 g/60 ml) was added to the reaction mixture, which was stirred by ice-cooling for about 1 hour. The crystals were collected by filtration and washed with an ice-cooled mixture of ethanol-water (1:1). The crystals thus obtained were treated with a mixture of ethanol-water (9:1, 100 ml), heated (70-80°C)and stirred so that the crystals were dissolved, then the insoluble matters were removed by hot filtration. The filtrate was ice-cooled for crystallization, and the crystals were collected by filtration, washed with ice-cooled ethanol-water mixture (8:2) and dried in vaccuo, to give white needles of 2-[[3-methyl-4-(2,2,2-trifluoro ethoxy)pyrid-2-yl]methylsulfinyl]benzimidazole (17.8 g). (yield: 89.5%). m.p. 177-178°C (decomposed)

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5578732, 1996, A
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP302720, 1989, A1

5
[ 1288338-69-1 ]
[ CAS Unavailable ]
[ 103577-45-3 ]

Yield	Reaction Conditions	Operation in experiment
93.2%	With dihydrogen peroxide; sodium thiosulfate In vanadium(V) oxide; dichloromethane; <i>tert</i>-butyl alcohol	1 EXAMPLE 1 EXAMPLE 1 2-[[3-Methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylthio]benzimidazole (monohydrate) (1.77 g) was dissolved in dichloromethane (30 ml), to which was added dropwise at 15°-20° C. a solution of hydrogen peroxide in t-butanol (2.75 ml corresponding to 0.2 g of hydrogen peroxide) containing vanadium pentaoxide (5 mg), and then allowed to react at 20°-25° C. for about one hour. After completion of the reaction, an aqueous solution of sodium thiosulfate (0.5 g/30 ml) was added to the reaction mixture, which was stirred vigorously for about 10 minutes, allowed to stand still, and separated into layers. The dichloromethane layer was washed with water (30 ml), and concentrated under reduced pressure; to the residue was added a mixture of ethanol-water (9:1, 10 ml) for crystallization. This solution was ice-cooled, and the crystals were collected by filtration and washed with an ice-cooled mixture of ethanol-water (8:2). The crystals thus obtained were treated with a mixture of ethanol-water (9:1, 10 ml), heated (65°-70° C.) and stirred for dissolution of the crystals, then the insoluble matters were removed by hot filtration. The filtrate was ice-cooled for crystallization, and the crystals were collected by filtration, washed with ice-cooled ethanol-water mixture (8:2) and dried in vacuo to give white crystals of 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylsulfinyl]benzimidazole (1.64 g). (yield: 93.2%). m.p. 177°-178° C. (decomposed)
93.2%	With dihydrogen peroxide; sodium thiosulfate In vanadium(V) oxide; dichloromethane; <i>tert</i>-butyl alcohol	1 Example 1 Example 1 2-[[3-Methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylthio]benzimidazole (monohydrate) (1.77 g) was dissolved in dichloromethane (30 ml), to which was added dropwise at 15-20°C a solution of hydrogen peroxide in t-butanol (2.75 ml corresponding to 0.2 g of hydrogen peroxide) containing vanadium pentaoxide (5 mg), and then allowed to react at 20-25°C for about one hour. After completion of the reaction,an aqueous solution of sodium thiosulfate (0.5 g/30 ml) was added to the reaction mixture, which was stirred vigorously for about 10 minutes, allowed to stand still, and separated into layers. The dichloromethane layer was washed with water (30 ml), and concentrated under reduced pressure; to the residue was added a mixture of ethanol-water (9:1, 10 ml) for crystallization. This solution was ice-cooled, and the crystals were collected by filtration and washed with an ice-cooled mixture of ethanol-water (8:2). The crystals thus obtained were treated with a mixture of ethanol-water (9:1, 10 ml), heated (65-70°C) and stirred for dissolution of the crystals, then the insoluble matters were removed by hot filtration. The filtrate was ice-cooled for crystallization, and the crystals were collected by filtration, washed with ice-cooled ethanol-water mixture (8:2) and dried in vaccuo to give white crystals of 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylsulfinyl]benzimidazole (1.64 g). (yield: 93.2%). m.p. 177-178°C (decomposed)
	With sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid In ethanol; chloroform	6 EXAMPLE 6 EXAMPLE 6 According to the same method as in Example 4, the following compounds were produced and analyzed by HPLC under the same conditions as in Example 5; the results are summarized as follows. STR7 2-[[3-Methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylthio]benzimidazole (monohydrate) (20 g) was dissolved in chloroform (200 ml), to which was added slowly dropwise below 5° C. a solution of m-chloroperbenzoic acid (13.5 g) in chloroform (200 ml), and stirred at the same temperature for about 10 minutes. After completion of the reaction, the reaction mixture was washed with a solution of sodium hydrogencarbonate, and dried over magnesium sulfate, and chloroform was evaporated off under reduced pressure. To the residue was added ethanol (100 ml) for crystallization, which was ice-cooled; the resulting crystals were collected by filtration and washed with ice-cooled ethanol. The crystals thus obtained were treated with a mixture of ethanol-water (9:1, 90 ml), heated (65°-70° C.) and stirred so that the crystals were dissolved, then the insoluble matters were removed by hot filtration. The filtrate was ice-cooled for crystallization and the crystals were collected by filtration, washed with ice-cooled ethanol-water mixture (8:2), and dried in vacuo, to give white needles of 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylsulfinyl]benzimidazole (14.9 g, yield: 74.9%). m.p. 177°-178° C. (decomposed)

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5578732, 1996, A
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP302720, 1989, A1
[3]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5578732, 1996, A

6
[ CAS Unavailable ]
[ 1288338-69-1 ]
[ CAS Unavailable ]
[ 103577-45-3 ]

Yield	Reaction Conditions	Operation in experiment
90.5%	With dihydrogen peroxide; sodium thiosulfate In ethanol	2 EXAMPLE 2 EXAMPLE 2 2-[[3-Methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylthio]benzimidazole (monohydrate) (10.0 g) was dissolved in ethanol (75 ml), to which was added a solution of sodium metavanadate (15 mg) in 35% aqueous solution of hydrogen peroxide (3.07 g), and allowed to react by stirring at 20°-25° for about 8 hours. After completion of the reaction an aqueous solution of sodium thiosulfate (1 g/5 ml) was added to the reaction mixture, which was stirred vigorously for about 10 minutes. The crystals were collected by filtration and washed with an ice-cooled mixture of ethanol-water (1:1). The crystals thus obtained were treated with a mixture of ethanol-water (9:1, 50 ml), heated (65°-70° C.) and stirred so that the crystals were dissolved, then the insoluble matters were removed by hot filtration. The filtrate was ice-cooled for crystallization, and the crystals were collected by filtration, washed with ice-cooled ethanol-water mixture (8:2) and dried in vacuo, to give white needles of 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylsulfinyl]benzimidazole (9.0 g). (yield: 90.5%). m.p. 177°-178° C. (decomposed)
90.5%	With dihydrogen peroxide; sodium thiosulfate In ethanol	2 Example 2 Example 2 2-[[3-Methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylthio]benzimidazole (monohydrate) (10.0 g) was dissolved in ethanol (75 ml), to which was added a solution of sodium metavanadate (15 mg) in 35% aqueous solution of hydrogen peroxide(3.07 g), and allowed to react by stirring at 20-25° for about 8 hours. After completion of the reaction an aqueous solution of sodium thiosulfate (1 g/5 ml) was added to the reaction mixture, which was stirred vigorously for about 10 minutes. The crystals were collected by filtration and washed with an ice-cooled mixture of ethanol-water (1:1). The crystals thus obtained were treated with a mixture of ethanol-water (9:1, 50 ml), heated (65-70°C) and stirred so that the crystals were dissolved, then the insoluble matters were removed by hot filtration. The filtrate was ice-cooled for crystallization, and the crystals were collected by filtration, washed with ice-cooled ethanol-water mixture (8:2) and dried in vaccuo, to give white needles of 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylsulfinyl]benzimidazole (9.0 g). (yield: 90.5%). m.p. 177-178°C (decomposed)

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5578732, 1996, A
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP302720, 1989, A1

7
[ 1288338-69-1 ]
[ CAS Unavailable ]
[ CAS Unavailable ]
[ 103577-45-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	With dihydrogen peroxide; sodium thiosulfate In ethanol	4 EXAMPLE 4 EXAMPLE 4 Vanadium(IV) acetylacetonate (40 mg) was dissolved in ethanol (150 ml), to which 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylthio]benzimidazole (monohydrate) (20.0 g) was added and then 35% aqueous solution of hydrogen peroxide (6.14 g) was added dropwise at 20°-25° C., and the mixture was allowed to react at 20°-25° C. for about 5 hours. After completion of the reaction, a solution of sodium thiosulfate (2.7 g/16 ml) was added to the reaction mixture and stirred vigorously for about 10 minutes. The crystals were collected by filtration and washed with an ice-cooled mixture of ethanol-water (8:2). The crystals thus obtained were treated with a mixture of ethanol-water (9:1, 90 ml), heated (60°-70° C.), and stirred so that the crystals were dissolved, then the insoluble matters were removed by hot filtration. The filtrate was ice-cooled for crystallization and the crystals were collected by filtration, washed with ice-cooled ethanol-water mixture (8:2) and dried in vacuo, to give white needles of 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylsulfinyl]benzimidazole (18.1 g). (yield: 91.0%). m.p. 177°-178° C. (decomposed)
91%	With dihydrogen peroxide; sodium thiosulfate In ethanol	4 Example 4 Example 4 Vanadium(IV) acetylacetonate (40 mg) was dissolved in ethanol (150 ml), to which 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]]methylthio]benzimidazole (monohydrate) (20.0 g) was added and then 35% aqueous solution of hydrogen peroxide (6.14 g) was added dropwise at 20-25°C, and the mixture was allowed to react at 20-25°C for about 5 hours. After completion of the reaction, a solution of sodium thiosulfate (2.7 g/16 ml) was added to the reaction mixture and stirred vigorously for about 10 minutes. The crystals were collected by filtration and washed with an ice-cooled mixture of ethanol-water (8:2). The crystals thus obtained were treated with a mixture of ethanol-water (9:1, 90 ml), heated (60-70°C) and stirred so that the crystals were dissolved, then the insoluble matters were removed by hot filtration. The filtrate was ice-cooled for crystallization and the crystals were collected by filtration, washed with ice-cooled ethanol-water mixture (8:2) and dried in vaccuo, to give white needles of 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2-yl]methylsulfinyl]benzimidazole (18.1 g). (yield: 91.0%). m.p. 177-178°C (decomposed)

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5578732, 1996, A
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP302720, 1989, A1

8
[ 127337-60-4 ]
[ 103577-45-3 ]
[ 1083100-26-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydroxide In water Heating;

Reference： [1]Reddy, Ganta Madhusudhan; Mukkanti; Kumar, T. Laxmi; Babu, J. Moses; Reddy, Padi Pratap [Synthetic Communications, 2008, vol. 38, # 20, p. 3477 - 3489]

9
[ 3967-54-2 ]
[ 103577-45-3 ]
4-[2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazol-1-yl]-1,3-dioxolan-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: lansoprasole With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 4-chloro-1,3-dioxolan-2-one With lithium iodide for 2h;	28 Example 28; 4-[2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazol-1-yl]-1,3-dioxolan-2-one To a solution (50 mL) of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole (2.0 g) in tetrahydrofuran was added sodium hydride (249 mg, 60% in oil) under ice-cooling after washing with hexane. The mixture was stirred at 0°C for 30 min. and lithium iodide (2.05 g) and chloroethylene carbonate (1.38 g) were added. The mixture was stirred for 2 hrs. The reaction solution was extracted with ethyl acetate - water, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluted with ethyl acetate), and recrystallized from ethyl acetate to give a less polar diastereomer (racemate, 860 mg) of the title compound as a colorless solid.1H-NMR (CDCl3) : 2.19(3H,s), 4.41(2H,q,J=8.0Hz), 4.75-5.00(4H,m), 6.67(1H,d,J=5.8Hz), 7.30-7.50(3H,m), 7.80-7.90(2H,m), 8.23(1H,d,J=5.8Hz).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1437352, 2004, A1 Location in patent: Page 46

10
[ 95061-46-4 ]
[ 103577-45-3 ]
(R)-(+)-lansoprazole (R)-(+)-1,1,2-triphenyl-1,2-ethanediol complex [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In chloroform; at 20℃;Reflux;Product distribution / selectivity;	Example 1 40.0 g (108.3 mmol) of racemic lansoprazole and 62.9 g (216.6 mmol: optical purity 99.7%ee) of (R)-(+)-l,l,2-triphenyl-l,2-ethanediol were suspended in 640 niL of chloroform, and refluxed until they were dissolved. The resulting mixture was slowly cooled to room temperature, stirred for 4 hours, and the precipitate formed was isolated by filtering, washed with cold chloroform, and dried at 400C, to obtain 41.1 g (80%) of the compound of formula (I) as a white crystalline powder (step A).Melting point: 147.8~149.9C Optical purity: 97.2%eeSpecific optical rotation: [alpha]D25 = +174.32 (c=1.0, MeOH)15 g (optical purity: 97.2%ee) of the complex thus obtained was added to 120 mL of chloroform, and the resulting mixture was refluxed until the complex was dissolved. Then, 180 mL of hexane was added thereto, slowly cooled to room temperature, stirred for 1 hour, and the precipitate formed was filtered, dried at 400C, to obtain 12 g (80%) of the compound of formula (I) as a white crystalline powder.Melting point: 149.6~151.4C Optical purity: >99.9%eeSpecific optical rotation: [alpha]D25 = +182.76 (c=1.0, MeOH) 1H-NMR (CDCl3, ppm): delta 8.24(d, IH), 7.68(d, 2H), 7.34~7.39(m, 4H),7.28-7.3 l(m, 4H), 7.04-7.16(m, 22H), 6.63(d, IH), 5.63(s, 2H), 4.64~4.80(q, 2H), 4.32~4.39(q, 2H), 3.36(s, 2H), 2.20(s, 3H)IR (KBr, cm"1): 3541, 3390, 3228, 3087, 3058, 3027, 2965, 2886, 2817, 2699, 1950, 1815, 1584, 1492, 1474, 1448, 1379, 1345, 1320, 1174, 1113, 1042, 1003, 974, 962, 929, 896, 760, 736, 696, 387

Reference： [1]Patent: WO2010/68049,2010,A2 .Location in patent: Page/Page column 6

11
[ 18531-94-7 ]
[ 103577-45-3 ]
(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole R-(+)-2,2'-dihydroxy-1,1'-binaphthyl [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.55%	In dichloromethane at 20 - 40℃; Resolution of racemate;	EXAMPLE 1Resolution of (R)-2-[[[3-methyl-4-(2,2,2-trifiuoroethoxy)-2-pridinyl-1] methyl] sulfinyI]-1H-benzimidazoIe (R-(+)-Lansoprazole) from racemic Lansoprazole.2-[[[3-methyl-4-(2,2,2-trifiuoroethoxy)-2-pridinyl-l]methyl]sulfinyl]-lH- benzimidazole (racemic lansoprazole) (200 gm, 0.542 moles) and R-(+)-BINOL (232.52 gm, 0.813 moles) were dissolved in methylene dichloride (7 L) at room temperature in a 10 L flask and heated to 35-40° C, under stirring, to obtain a clear solution. The reaction mixture was concentrated under vacuum below 35° C until the volume of the reaction mixture was approximately 5-6 times with respect to lansoprazole. Toluene (5760 ml) was charged to the reaction mixture, which was cooled to about 20-25° C. n-Hexane (1440 ml) was then added and the temperature was maintained between 20° C and 25° C. The reaction mixture was then cooled to 0-5° C and stirred at this temperature for 12 hours. The crystallized product was filtered and washed with n-hexane and suck-dried to obtain 230 gm of crude R-(+)-lansoprazole - R-(+)-BINOL inclusion complex.Purification of crude complexThe crude R-(+)-lansoprazole - R-(+)-BINOL inclusion complex was dissolved in 3000 ml methylene dichloride and concentrated under vacuum maintaining the temperature below 35° C until the volume of the reaction mixture was about 5-6 times with respect to lansoprazole. Toluene (5760 ml) was charged to reaction mixture and the reaction mixture was cooled to about 20-25° C. n-Hexane (1440 ml) was added, maintaining the temperature between 20° C and 25° C. The reaction mixture was then cooled to 0-5° C and stirred at this temperature for 12 hours. The crystallized product was filtered and washed with n-hexane. The wet product was dried at 40° C under vacuum to obtain 185 gm of pure R-(+)-lansoprazole - R-(+)-BINOL inclusion complex.Chiral purity by HPLC > 97% e.e.Yield: 92.55 % w/w
92.55%	In dichloromethane at 20 - 40℃;	1 Example 1; Resolution of (R)-2-[[[3-methyl-4-(2,2,2-trifiuoroethoxy)-2-pridinyl-1]methyl]sulfinyl]-1H-benzimidazole (R-(+)-Lansoprazole) from racemic Lansoprazole.2-[[[3-methyl-4-(2,2,2-trifiuoroethoxy)-2-pridinyl-1]methyl]sulfinyl]-1H-benzimidazole (racemic Lansoprazole) (200 gm, 0.542 moles) and R-(+)-BINOL (232.52 gm, 0.813 moles) was dissolved in methylene dichloride (7 L) at room temperature in a 10 L flask and heated to 35-40° C., under stirring, to get a clear solution. The reaction mixture was concentrated under vacuum below 35° C. until the volume of the reaction mixture was approximately 5-6 times with respect to lansoprazole. Toluene (5760 ml) was charged to the reaction mixture, which was cooled to about 20-25° C. n-Hexane (1440 ml) was then added and the temperature was maintained between 20° C. and 25° C. The reaction mixture was then cooled to 0-5° C. and stirred at this temperature for 12 hours. The crystallized product was filtered and washed with n-hexane and suck-dried to obtain 230 gm of crude R-(+)-lansoprazole-R-(+)-BINOL inclusion complex.Purification of Crude ComplexThe crude R-(+)-lansoprazole-R-(+)-BINOL inclusion complex was dissolved in 3000 ml methylene dichloride and concentrated under vacuum maintaining the temperature below 35° C. until the volume of the reaction mixture was about 5-6 times with respect to lansoprazole. Toluene (5760 ml) was charged to reaction mixture and the reaction mixture was cooled to about 20-25° C. n-Hexane (1440 ml) was added maintaining the temperature between 20° C. and 25° C. The reaction mixture was then cooled to 0-5° C. and stirred at this temperature for 12 hours. The crystallized product was filtered and washed with n-hexane. The wet product was dried at 40° C. under vacuum to get 185 gm of pure R-(+)-lansoprazole-R-(+)-BINOL inclusion complexChiral purity by HPLC>97% eeYield: 92.55% w/w
92.55%	In dichloromethane at 20 - 40℃;	1 Example 1Resolution of (R)-2-[[[3-Methyl-4-(2,2,2-Trifiuoroethoxy)-2-Pridinyl-1]Methyl] Sulfinyl]-1H-Benzimidazole (R-(+)-Lansoprazole) from Racemic Lansoprazole2-[[[3-methyl-4-(2,2,2-trifiuoroethoxy)-2-pridinyl-1]methyl]sulfinyl]-1H-benzimidazole (racemic lansoprazole) (200 gm, 0.542 moles) and R-(+)-BINOL (232.52 gm, 0.813 moles) were dissolved in methylene dichloride (7 L) at room temperature in a 10 L flask and heated to 35-40° C., under stirring, to obtain a clear solution. The reaction mixture was concentrated under vacuum below 35° C. until the volume of the reaction mixture was approximately 5-6 times with respect to lansoprazole. Toluene (5760 ml) was charged to the reaction mixture, which was cooled to about 20-25° C. n-Hexane (1440 ml) was then added and the temperature was maintained between 20° C. and 25° C. The reaction mixture was then cooled to 0-5° C. and stirred at this temperature for 12 hours. The crystallized product was filtered and washed with n-hexane and suck-dried to obtain 230 gm of crude R-(+)-lansoprazole-R-(+)-BINOL inclusion complex.Purification of Crude ComplexThe crude R-(+)-lansoprazole-R-(+)-BINOL inclusion complex was dissolved in 3000 ml methylene dichloride and concentrated under vacuum maintaining the temperature below 35° C. until the volume of the reaction mixture was about 5-6 times with respect to lansoprazole. Toluene (5760 ml) was charged to reaction mixture and the reaction mixture was cooled to about 20-25° C. n-Hexane (1440 ml) was added, maintaining the temperature between 20° C. and 25° C. The reaction mixture was then cooled to 0-5° C. and stirred at this temperature for 12 hours. The crystallized product was filtered and washed with n-hexane. The wet product was dried at 40° C. under vacuum to obtain 185 gm of pure R-(+)-lansoprazole-R-(+)-BINOL inclusion complex.Chiral purity by HPLC>97% e.e.Yield: 92.55% w/w

Reference： [1]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - WO2010/79504, 2010, A2 Location in patent: Page/Page column 10; 11
[2]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - US2010/280077, 2010, A1 Location in patent: Page/Page column 2
[3]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - US2011/65755, 2011, A1 Location in patent: Page/Page column 3

12
[ 127337-60-4 ]
[ 583-39-1 ]
[ 103577-45-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: 3-methyl-4-(2,2,2-trifluoroethoxy)-2-chloromethylpyridine hydrochloride; 1H-benzo[d]imidazole-2-thiol With chloro-carboxylic acid; anhydrous sodium carbonate In methanol at 64℃; for 3h; Stage #2: With titanium isopropoxide In lithium hydroxide monohydrate; toluene at 28 - 55℃; for 1.83333h; Further stages;	1 92A step, taking 105.3g anhydrous sodium carbonate was added 1.2L of anhydrous methanol, stirred open, chloroformate was added 124.3g 2- Ethoxy-3-methyl-4-trifluoromethyl pyridine hydrochloride and 66.75g 2- mercapto - benzimidazole After the addition reaction was heated to 64 ° C, 3h heating was stopped and cooled to room temperature (25 ° C), insoluble material was removed by filtration, the filtrate was concentrated under reduced pressure to about 200g, filtered, the filter Cake was washed with a small amount of anhydrous methanol, and the filtrate was concentrated until no liquid drops out, the remaining yellow viscous 200ml of toluene was added, Stirred at room temperature (25 ° C) down to the muddy, the solution was concentrated under reduced pressure to 251g, continued at room temperature (25 ° C) stirred crystallization, 6h after Filtered, the filter cake was washed with 70ml of toluene to give an off-white solid 146.2g, yield 92%;Step two, take 570ml of toluene was heated to 28 ° C, was added 44.29g of tetraisopropyl titanate was stirred for 30 minutes, 118g above white solids and water, continue stirring 28 ° C for 20 minutes, the reaction was heated to 55 ° C 1h, stop heating, Cooled to 28 ° C, was added 21.41g N, N- diisopropylethylamine, dropwise 66.49ml 70% (mass% concentration) of 570ml 12.5% was added to the reaction mixture after the hydrogen peroxide, cumene increase after the 28 ° C reaction 1.2h, the reaction was stopped (Mass percentage) of ammonia, liquid separation, the organic phase was 2 * 570ml 12.5% (mass% concentration) of ammonia And the combined aqueous phase was 398.0ml acetic acid to a pH of about 7.0, and extracted with 500ml methylene chloride, the aqueous layer was then 2 * 250 ml dichloromethane and the combined organic phases, the organic phase is 0.06MPa, the degree of vacuum, a temperature of 45 ° C recovering the organic solvent Agent to do, and then dried at 35 ° C to give 112.3g yellow solid in 91% yield;Step three, in 500mL with sealing stirrer, reflux condenser, dropping funnel and a thermometer clean four-necked flask Added above 25g yellow solid and 125mL acetone, mixing completely, heated to 54 ° C, heat stirring 30min, To reduce the solid is not dissolved, filtered hot, filtered hot end, and the filtrate was added dropwise 75mL of purified water was added after cooling to 10 ° C, Incubated 2h, to give a white solid precipitate was filtered, the filter cake was rinsed with 24mL cold acetone, drained purified lansoprazole obtained Wet product, dried at 32 ° C to constant weight to give lansoprazole boutique 21.9g, HPLC purity of 99.89%, a yield of 98%;
98.1%	With sodium hydroxide In lithium hydroxide monohydrate at 58 - 70℃; for 5h;	1.1-1.6; 2.1-2.6; 3.1-3.6 Example 2 Test operation: 1. Add 23.6g of sodium hydroxide and 100ml of purified water to the beaker, stir until completely dissolved, then add 20.6g of 2-mercaptobenzimidazole, stir until completely dissolved, and pour it into a dropping funnel for later use.2. Add 20 g of 2-chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride and 120 ml of purified water to the four-necked flask, stir and heat up.3. The temperature was raised to 58°C, and the aqueous solution of 2-mercaptobenzimidazole sodium hydroxide was slowly added dropwise, and the temperature was controlled at 50-70°C, and the dropwise addition was completed in 75 minutes.4. Continue to incubate for 5 hours, the sampling point plate is controlled, and the remaining amount of 2-mercaptobenzimidazole is ≤ 0.1%.5. Start to cool down, the temperature drops to 20°C, and the temperature is kept at 15-25°C for 4 hours.6. After the insulation is completed, suction filter, put the wet product into the oven to dry,The temperature was set to 58° C., and dried for 10 h to obtain 26.4 g of lansoprazole intermediate H-benzimidazole.Yield=26.40.7435/20100%=98.1%.
95.3%	Stage #1: 3-methyl-4-(2,2,2-trifluoroethoxy)-2-chloromethylpyridine hydrochloride; 1H-benzo[d]imidazole-2-thiol With lithium hydroxide monohydrate; potassium hydroxide at 60℃; for 1h; Stage #2: With sodium chlorine monoxide; N-benzyl-N,N,N-trimethyl-ammonium chloride; sodium hydroxide In lithium hydroxide monohydrate at -10 - 10℃; for 4h;	1-3 Preparation of lansoprazole crude product Add 68 g of 2-mercaptobenzimidazole, 40 g of drinking water and 56 g of potassium hydroxide into a 2L reaction flask, and stir at room temperature until it is clear. Prepare a solution of 125g lansoprazole chloride and 500g drinking water. The lansoprazole chloride aqueous solution was added dropwise to the reaction kettle at room temperature, and the dropping time was 1 to 2 hours. After the dropping, the temperature was raised to 60° C. and the reaction was stirred for 1 hour. The temperature was lowered to 10°C and lye prepared by 22g of sodium hydroxide and 88g of drinking water and 8.4g of trimethylbenzylammonium chloride were added. After the addition, 472g of 10% sodium hypochlorite aqueous solution was added dropwise at -10°C, and the dropping time was about 2h. After the addition was completed, the reaction was kept at 0°C for 2 hours and then sampled and analyzed. The residual lansoprazole sulfide was less than 2.0%. Prepare a solution of 8.3g sodium thiosulfate and 113g drinking water. After the reaction is completed, the temperature is controlled at -5 to 5°C, and sodium thiosulfate aqueous solution is added dropwise. After dripping, the mixture was stirred for about 20 minutes and then centrifuged. The filter cake was rinsed with drinking water to obtain the crude lansoprazole. The HPLC chart is shown in Figure 6, HPLC: 99.82%.Preparation of Lansoprazole PremiumThe crude lansoprazole was transferred to a 1L reaction flask, 300g isopropanol was added, the temperature was raised to 45°C and stirred for 1 hour, and then the temperature was lowered to 25°C and stirred for 1 hour. Ammonia gas was introduced for 5 minutes. At this time, the pH of the system was 77.8. , Cooling to 10 , stirring and crystallization for 2h. After filtering, the filter cake is rinsed with 50g of isopropanol cooled to 5-10°C to obtain a refined wet product of lansoprazole. Drying under a nitrogen atmosphere at 40°C for 13 hours yielded 159.9 g of lansoprazole as a dry product, with a total molar yield: 95.3%. The HPLC chart is shown in Figure 7, and the HPLC: 99.99%.

Reference： [1]Current Patent Assignee: SHANGHAI TITAN TECHNOLOGY - CN104447696, 2016, B Location in patent: Paragraph 0016-0020
[2]Current Patent Assignee: SHANDONG KEYUAN PHARMACEUTICAL - CN114853678, 2022, A Location in patent: Paragraph 0039-0067
[3]Current Patent Assignee: NANJING GUOXING BIOTECHNOLOGY RES INSTITUTE - CN112707889, 2021, A Location in patent: Paragraph 0047-0075

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A280146[ 226904-00-3 ]

Sodium 2-(((3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide

Reason: Free-salt

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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. 103577-45-3 ] {[proInfo.proName]}

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[ 103577-45-3 ] Synthesis Path-Downstream 1~12

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