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CAS No. : | 202409-33-4 | MDL No. : | MFCD06797512 |
Formula : | C18H15ClN2O2S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MNJVRJDLRVPLFE-UHFFFAOYSA-N |
M.W : | 358.84 | Pubchem ID : | 123619 |
Synonyms : |
MK-0663;L-791456;Etoricoxib, Arcoxia, L-791456, MK 0663, MK-0663;Nucoxia;Algix;Tauxib;MK-663;Arcoxia
|
Num. heavy atoms : | 24 |
Num. arom. heavy atoms : | 18 |
Fraction Csp3 : | 0.11 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 95.97 |
TPSA : | 68.3 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | Yes |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -6.12 cm/s |
Log Po/w (iLOGP) : | 2.75 |
Log Po/w (XLOGP3) : | 3.34 |
Log Po/w (WLOGP) : | 5.26 |
Log Po/w (MLOGP) : | 2.48 |
Log Po/w (SILICOS-IT) : | 4.41 |
Consensus Log Po/w : | 3.65 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -4.53 |
Solubility : | 0.0107 mg/ml ; 0.0000298 mol/l |
Class : | Moderately soluble |
Log S (Ali) : | -4.45 |
Solubility : | 0.0127 mg/ml ; 0.0000354 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -7.96 |
Solubility : | 0.00000397 mg/ml ; 0.0000000111 mol/l |
Class : | Poorly soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.96 |
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P262-P270-P280-P302+P352+P310 | UN#: | 2811 |
Hazard Statements: | H301 | Packing Group: | Ⅱ |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.1% | With ammonium hydroxide; In tetrahydrofuran; at 60 - 65℃;Inert atmosphere; | 1.3) The compound AYTKX04 obtained in the step 1.2) was charged into a 20 L reaction vessel, 2812 ml of THF was added, concentrated aqueous ammonia (1158.5 g, 17.01 mol) was added dropwise, and after the addition was completed, the mixture was heated to 60-65 C for 3-4 h, and the TLC showed basic The reaction is complete, and the liquid is allowed to stand still. 5600 ml of a 3% aqueous solution of sodium hydrogencarbonate was added dropwise to the organic phase, and a solid was precipitated, and the mixture was stirred under cooling, and stirred at 5 to 10 C for about 1 hour. Filter by suction, wash with 1000ml THF/H2O (1:2 (v/v)) mixed solution, vacuum dry at 40-45 C to constant weight, Obtained 629.0 yellow solid, That is, etoricoxib (Compound AYTKX05), the yield was 72.1%. The total content of impurity F, impurity 20 and impurity 21 in AYTKX05 was determined to be 0.0072%, and the content of impurity M was 0.0107%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With dioxouranium(VI) acetate hydrate; o-xylene; oxygen; In water; acetonitrile; for 24h;Irradiation; | General procedure: In a 25mL reaction tube, add uranyl acetate hydrate (1.7mg, 4 * 10-3mmol),4-methylphenyl (n-butyl) sulfide (36.0 mg, 0.2 mmol), water (36 mg, 2 mmol), o-xylene (0.2 mL), acetonitrile (1 mL), evacuate for oxygen,Stir for 24 hours under three 2 watt LED lights,After the reaction is completed, it is dried, filtered, and concentrated.Column chromatography (PE / EA = 2/1) separated as colorless liquid 3a (39.0 mg, 92%) |
87% | EXAMPLE 1 FORM V OF 5-CHLORO-3-(4-METHANESULFONYLPHENYL)-6'-METHYL-[2,3']BIPYRIDINYL A mixture of Preparative Example H and isopropyl acetate (IPAC) was heated at 55 C. The suspension was cooled to ambient temperature and the solids were isolated by filtration. The solids were washed with IPAC and dried in vacuo to give the Form V polymorph (1.1 kg) as a colorless solid in ~87% yield. 1H NMR (400 MHz CDCl3) delta8.69 (d, 1H, J=2.3 Hz), 8.36 (3, 1H, J=2.2 Hz), 7.88 (d, 2H, J=8.4 Hz), 7.72 (d, 1H, J=2.3 Hz), 7.54 (dd, 1H, J1=8.0 Hz, J2=2.3 Hz), 7.38 (d, 2H, J=8.5 Hz), 7.07 (d, 1H, J=8.0 Hz), 3.06 (s, 3H), 2.51 (s, 3H); 13C NMR (100 MHz CDCl3) delta158.4, 152.2, 149.7, 148.3, 143.7, 140.1, 137.9, 137.2, 135.18. 131.1, 130.0, 130.3, 127.8, 122.7, 44.4, 24.1. | |
A family of specific compounds within Formula 1 of particular interest include compounds and pharmaceutically-acceptable salts thereof, as follows: C1) 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; 5-chloro-3-(4-(methylsulfonyl)phenyl)-2-(methyl-5-pyridinyl)pyridine; 2-(3,5-difluorophenyl)-3-4-(methylsulfonyl)phenyl)-2-cyclopenten-1-one; 2-(6-methylpyrid-3-yl)-3-(4-methylsulfinylphenyl)-5-chloropyridine. |
Additional specific compounds of particular interest within Formula I include each of the compounds and pharmaceutically-acceptable salts thereof as follows: ... 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide, 4-(4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone, 4-[5-(4-chorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzenesulfonamide, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide, 5-chloro-3-(4-(methylsulfonyl)phenyl)-2-(methyl-5-pyridinyl)pyridine, 2-(3,5-difluorophenyl)-3-4-(methylsulfonyl)phenyl2-cyclopenten-1-one, 4-(4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone, 4-[5-methyl-3-phenyl-isoxazol-4-yl]benzenesulfonamide, and ... | ||
6-[[5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrol-2-yl]methyl]-3(2H)-pyridazinone or RS 57067 (D-2); ... celecoxib (D-18); valdecoxib (D-19); deracoxib (D-20); rofecoxib (D-21); etoricoxib (D-22); parecoxib (D-24) | ||
wherein the cyclooxygenase-2 selective inhibiting compound is selected from the group consisting of: ... deracoxib; valdecoxib; parecoxib; rofecoxib; etoricoxib; meloxicam; lumiracoxib; 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; ... | ||
Some individual compounds within Formula 1, each of which are of particular interest in the present invention include compounds and pharmaceutically-acceptable salts thereof, as follows: ... e. 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide (JTE-522). f. 2-(6-methylpyrid-3-yl)-3-(4-methylsulfinylphenyl)-5-chloropyridine (etoricoxib). g. 5-chloro-3-(4-(methylsulfonyl)phenyl)-2-(methyl-5-pyridinyl)pyridine. h. 2-(3,5-difluorophenyl)-3-4-(methylsulfonyl)phenyl)-2-cyclopenten-1-one. ... | ||
claim 11 wherein the COX-2 selective inhibiting agent is selected from: ... 5-Chloro-2-(4-chlorophenyl)-3-(4-methylsulfonyl) phenylpyridine; 5-Chloro-3-(4-methylsulfonyl)phenyl-2-(2-pyridinyl) pyridine; 5-Chloro-3-(4-methylsulfonyl)phenyl-2-(3-pyridinyl) pyridine; 5-Chloro-3-(4-methylsulfonyl)phenyl-2-(4-pyridinyl) pyridine; 5-Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine; 2-(4-Chlorophenyl)-3-(4-methylsulfonyl)phenylpyridinyl-5-carboxylic acid methyl ester; 2-(4-Chlorophenyl)-3-(4-methylsulfonyl)phenylpyridinyl-5-carboxylic acid; 5-Cyano-2-(4-chlorophenyl)-3-(4-methylsulfonyl) phenylpyridine; ... | ||
A family within Formula 1 which are particularly preferred include the following compounds and their pharmaceutically-acceptable salts: ... 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide (celecoxib), 4-[5-methyl-3-phenyl-3-phenylisoxazol-4-yl]benzensulfonamide (valdecoxib), 4-[5-(3-fluoro-4mthoxyphenyl)-3-difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (deracoxib), 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide (JTE-522), 5-chloro-3-(4-(methylsulfonyl)phenyl)-2-(methyl-5-pyridinyl)pyridine, 2-(3,5-difluorophenyl)-3-4-(methylsulfonyl)phenyl)-2-cyclopenten-1-one, N-[[4-(5-methyl-3-phenylisoxazol-4yl]phenyl]sulfonyl]propanamide, 4-[5-(4-chorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzenesulfonamide, ... | ||
wherein the selective COX-2 inhibiting agent is selected from the group consisting of rofecoxib, celecoxib, valdecoxib, deracoxib, etoricoxib, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide, 5-chloro-3-(4-(methylsulfonyl)phenyl)-2-(methyl-5-pyridinyl)pyridine, 2-(3,5-difluorophenyl)-3-4-(methylsulfonyl)phenyl)-2-cyclopenten-1-one, N-[[4-(5-methyl-3-phenylisoxazol-4yl]phenyl]sulfonyl]propanamide, ... | ||
wherein the selective COX-2 inhibiting agent is selected from the group consisting of ... valdecoxib, deracoxib, etoricoxib, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide, 5-chloro-3-(4-(methylsulfonyl)phenyl)-2-(methyl-5-pyridinyl)pyridine, 2-(3,5-difluorophenyl)-3-4-(methylsulfonyl)phenyl)-2-cyclopenten-1-one, N-[[4-(5-methyl-3-phenylisoxazol-4yl]phenyl]sulfonyl]propanamide, 4-[5-(4-chorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzenesulfonamide, ... | ||
The compound of formula (B) CS-502 [Chemical Abstracts Service Registry Number ("CAS Reg. No.") 176429-82-6]; (6aR,10aR)-3-(1,1-dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-carboxylic acid ("CT-3"); 2(5H)-Furanone, 5,5-dimethyl-3-(1-methylethoxy)-4-[4-(methylsulfonyl)phenyl]-("DFP"); Etoricoxib, | ||
The compound of formula (B) CS-502 [Chemical Abstracts Service Registry Number ("CAS Reg. No.") 176429-82-6]; (6aR,10aR)-3-(1,1-dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-carboxylic acid ("CT-3"); 2(5H)-Furanone, 5,5-dimethyl-3-(1-methylethoxy)-4-[4-(methylsulfonyl)phenyl]-("DFP"); Etoricoxib; Lumiracoxib (tradename "PREXIGE"); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
tetrakis(triphenylphosphine) palladium(0); | Step 3: 5-Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridyl)pyridine A mixture of 2,5-dichloro-3-(4-methylsulfonyl)phenylpyridine from Example 20, Step 5 (750 mg), 2-methyl-5-trimethylstannylpyridine (1.3 g) and palladium tetrakis(triphenylphosphine) (290 mg) in NMP (10 mL) was heated at 100 C. for 15 h. The mixture was cooled to r.t., diluted with ethyl acetate and filtered through a bed of celite. The filtrate was washed with water, twice with 5% potassium fluoride and then extracted with 1N HCl. The aqueous phase was neutralized with 10N sodium hydroxide and then extracted with ethyl acetate. The organics were concentrated and the residue subjected to flash chromatography (eluding with ethyl acetate) to provide the title compound as a white solid, m.p. 127-128 C. | |
tetrakis(triphenylphosphine) palladium(0); | Step 3 5-Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridyl)pyridine A mixture of 2,5-dichloro-3-(4-methylsulfonyl)phenyl-pyridine from Example 20, Step 5 (750 mg), 2-methyl-5-trimethyl-stannylpyridine (1.3 g) and palladium tetrakis(triphenylphosphine) (290 mg) in NMP (10 mL) was heated at 100 C. for 15 h. The mixture was cooled to r.t., diluted with ethyl acetate and filtered through a bed of celite. The filtrate was washed with water, twice with 5% potassium fluoride and then extracted with 1 N HCl. The aqueous phase was neutralized with 10 N sodium hydroxide and then extracted with ethyl acetate. The organics were concentrated and the residue subjected to flash chromatography (eluding with ethyl acetate) to provide the title compound as a white solid, m.p. 127-128 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In isopropyl alcohol; at 0 - 70℃;Reflux;Purification / work up; | Example-7Preparation of 5-chloro-3-[4-methylsulfonyl)phenyl]-2-(2-methyl-5-pyridinyl) pyridine, a compound of formula A, <strong>[202409-33-4]etoricoxib</strong>.In a 1L 4-neck round bottom flask equipped with overhead stirrer, double surface condenser, thermowell pocket placed in water bath, 720ml of isopropyl alcohol was added followed by 90.0gm <strong>[202409-33-4]etoricoxib</strong> crude prepared as per example 5 and heated the reaction mass to about 65C to about 70C.The reaction mass was charcoalised with NORIT charcoal and maintained at that temperature for about an hour. The reaction mass was hot filtered on a hyflo bed and washed with hot isopropyl alcohol. The filtrate was heated to reflux to obtain a clear solution. The filtrate was gradually cooled to about 25C to about 30C with intermittent stirring, wherein the stirring was performed once in every 30 minutes and then further cooled to about 0C to about 5C and maintained for about an hour and then filtered and washed with isopropyl alcohol. The wet solids were dried in an air oven. <strong>[202409-33-4]Etoricoxib</strong> 80gm was obtained.HPLC purity: 99.89%furan impurity less than 0.1% andparticle size distribution: dl0=2.64mum., d50= 1 1.46mu?iota., d90 =54.65 mu?iota. | |
Example-23Purification of 5-Chloro-3-(4-methylsulphonyl) phenyl-2-(2-methyl-5-pyridinyl) pyridine, <strong>[202409-33-4]Etoricoxib</strong> (I)<strong>[202409-33-4]Etoricoxib</strong> (I), as obtained in example 19 was purified by crystallization form aqueous isopropanol. The compound (20 gms) was dissolved isopropanol (90 ml) containing 4%w/w water at reflux temperature under stirring. Activated carbon (1.9 gms) was added and the product solution was filtered after 15-20 minutes of reflux. Filtrate was cooled slowly to ambient temperature and then to 12-15C for about 1 hour. Crystallized product was collected by filtration followed by washing with chilled isopropanol (5-10 ml). The mass was dried at 60-70C to get light creamish product (yield 14.0 gms, m.p.l34-137,HPLC purity 99.40%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetone; toluene; at 20 - 55℃; | Toluene (3.6 ml), acetone (1.4 ml) and <strong>[202409-33-4]etoricoxib</strong> (0.5 g) were taken into a reaction flask, the mixture was heated at 50-55C, followed by the addition of p-toluenesulfonic acid (0.5 g). The reaction mass was cooled to 20-25C, maintained for 24 hours and further cooled to 0- 5C for 3 hours. The solid obtained was filtered, washed with toluene (2 ml) and then dried at 50-55C for 1 hour to yield 0.35 g of crystalline <strong>[202409-33-4]etoricoxib</strong> tosylate (Purity by HPLC: 99.54%). | |
In ethyl acetate; at 55 - 60℃; | Example-26Purification of 5-Chloro-3-(4-methylsulphonyl) phenyl-2-(2-methyl-5-pyridinyl) pyridine, <strong>[202409-33-4]Etoricoxib</strong> (I)<strong>[202409-33-4]Etoricoxib</strong> (I) as obtained in example 19 (20 gms) was dissolved in ethyl acetate (110 ml) at ambient condition, under stirring. Paratoluenesulphonic acid (16 gms) was added to it slowly in small lots. The mass was heated to 55-60C to obtain a clear solution and then treated with 0.5gm active carbon for 15-20 minutes. The solution was filtered hot, and cooled under stirring to 10-12C for a period of about one hour. <strong>[202409-33-4]Etoricoxib</strong> paratoluenesulphonic acid salt was isolated by filtration, washed with chilled ethyl acetate (10 ml -15 ml), and dried at 50-60 till constant weight (yield 28 gm) | |
17.8 g | In acetone; for 16h; | Will rely on the crude Coxi (HPLC purity 85.17%) 21.8g,Add acetone (500 mL),A solution of p-toluenesulfonic acid (15.8 g) in acetone was added dropwise with stirring,After stirring, add p-toluenesulfonate for 16 hours.filter,Acetone leaching twice,50 C under vacuum to give 17.8 g of a yellow solid as etoposide p-toluenesulfonate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; at 20 - 55℃; | Toluene (5 ml) and <strong>[202409-33-4]etoricoxib</strong> (1 g) were taken into a reaction flask, the mixture was heated at 50-55C, followed by the addition of benzoic acid (0.45 g). The reaction mass was cooled to 20-25C and maintained for 12 hours. Toluene was distilled out completely from the reaction mass, followed by the addition of n-hexane and ethyl acetate (6 ml). The resulting mixture was stirred for 2 hours, followed by cooling to 0-5C. The solid obtained was filtered, washed with ethyl acetate (3 ml) and then dried at 50-55C for 1 hour to yield 1.15 g of crystalline <strong>[202409-33-4]etoricoxib</strong> benzoate (Purity by HPLC: 99.69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | In isopropyl alcohol; at 80℃; for 0.0833333h; | 10.0g of 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridinyl was dissolved in 50ml of isopropanol at 80C to give a slightly yellow solution. 3.3g of fumaric acid was added to the solution as a solid and dissolved, the solution was stirred for 5 minutes then cooled. A white solid precipitated from the solution at 30C to give a thick slurry. The slurry was cooled to 15 C and the solid was isolated by filtration and dried in a vacuum oven for a final yield of 10.3 g of the fumaric acid salt (78%). |
In toluene; at 20 - 55℃; | Toluene (5 ml) and <strong>[202409-33-4]etoricoxib</strong> (1 g) were taken into a reaction flask, the mixture was heated at 50-55C, followed by the addition of fumaric acid (0.40 g). The reaction mass was cooled to 20-25C and maintained for 2 hours. The solid obtained was filtered, washed with toluene (3 ml) and then dried at 50-55C for 1 hour to yield 1 g of crystalline <strong>[202409-33-4]etoricoxib</strong> fumarate salt (Purity by HPLC: 99.79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetone; toluene; at 20 - 55℃;Product distribution / selectivity; | Toluene (5 ml) and <strong>[202409-33-4]etoricoxib</strong> (1 g) were taken into a reaction flask, the mixture was heated at 50-55C. Oxalic acid (0.45 g) was added to the resulting mass, followed by the addition of acetone (3 ml). The reaction mass was cooled to 20-25C and maintained for 12 hours. The solid obtained was filtered, washed with toluene (2 ml) and then dried at 50-55C for 1 hour to produce 1.15 g of crystalline <strong>[202409-33-4]etoricoxib</strong> oxalate salt (Purity by HPLC: 99.52%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In isopropyl alcohol; at 80℃; for 0.25h; | 10.0g of 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridinyl was dissolved in 50ml of isopropanol at 80C to give a slightly yellow solution . 3.3g of succinic acid was added to the solution as a solid and dissolved, the solution was stirred for 15 minutes then cooled. A white solid precipitated from the solution at 30C to give a thick slurry. The solid was isolated by filtration and dried in a vacuum oven for a final yield of 10.8g of the succinic acid salt (81%). |
In toluene; at 20 - 55℃; | Toluene (5 ml) and <strong>[202409-33-4]etoricoxib</strong> (1 g) were taken into a reaction flask, the mixture was heated at 50-55C, followed by the addition of succinic acid (0.45 g). The reaction mass was cooled to 20-25C and maintained for 2 hours. The solid obtained was filtered, washed with toluene (3 ml) and then dried at 50-55C for 1 hour to yield 1.2 g of crystalline <strong>[202409-33-4]etoricoxib</strong> succinate (Purity by HPLC: 99.27%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; at 20 - 55℃;Product distribution / selectivity; | Toluene (5 ml) and <strong>[202409-33-4]etoricoxib</strong> (1 g) were taken into a reaction flask, the mixture was heated at 50-55C, followed by the addition of salicylic acid (0.5 g). The reaction mass was cooled to 20-25C and maintained for 2 hours. Toluene was distilled out completely from the reaction mass, followed by the addition of n-hexane (5 ml) and ethyl acetate (6 ml). The reaction mass was stirred for 2 hours and cooled to 0-5C. The solid obtained was filtered, washed with ethyl acetate (3 ml) and then dried at 50-55C for 1 hour to yield 1.13 g of <strong>[202409-33-4]etoricoxib</strong> salicylate crystalline form I (Purity by HPLC: 99.85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; at 20 - 55℃;Product distribution / selectivity; | Toluene (5 ml) and <strong>[202409-33-4]etoricoxib</strong> (1 g) were taken into a reaction flask, the mixture was heated at 50-55C, followed by the addition of cinnamic acid (0.45 g). The reaction mass was cooled to 20-25C and maintained for 12 hours. Toluene was distilled out completely from the reaction mass, followed by the addition of n-hexane and ethyl acetate (6 ml). The reaction mass was stirred for 2 hours and then cooled to 0-5C. The solid obtained was filtered, washed with ethyl acetate (3 ml) and then dried at 50-55C for 1 hour to yield 1.02 g of <strong>[202409-33-4]etoricoxib</strong> cinnamate crystalline form I (Purity by HPLC: 99.56%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; at 20 - 55℃; | Toluene (5 ml) and <strong>[202409-33-4]etoricoxib</strong> (1 g) were taken into a reaction flask, the mixture was heated at 50-55C, followed by the addition of glutamic acid (0.5 g). The reaction mass was cooled to 20-25C and maintained for 12 hours. The solid obtained was filtered, washed with toluene (5ml) and then dried at 50-55C for 1 hour to yield 1.1 g of crystalline <strong>[202409-33-4]etoricoxib</strong> glutamate (Purity by HPLC: 95.24%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; In water; isopropyl alcohol; at 20 - 30℃;Product distribution / selectivity; | Crude <strong>[202409-33-4]etoricoxib</strong> (3.5 g, the oily mass obtained according to reference example 1) was dissolved in isopropanol (10 ml) at 25-30C, followed by the addition of aqueous hydrobromic acid (2 ml) at 25-30C. The resulting mass was stirred for 2 to 3 hours, the resulting solid was filtered and then washed with isopropanol (3.5 ml). The resulting solid was dried under vacuum at 50-55C to give 1.5 g of <strong>[202409-33-4]etoricoxib</strong> hydrobromide crystalline Form II (HPLC Purity: 98.10%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With aminosulfonic acid; In toluene; at 20 - 55℃; | Toluene (5 ml) and <strong>[202409-33-4]etoricoxib</strong> (1 g) were taken into a reaction flask, the mixture was heated at 50-55C, followed by the addition of sulfamic acid (0.3 g). The reaction mass was cooled to 20-25C and maintained for 12 hours. The solid obtained was filtered, washed with toluene (4 ml) and then dried at 50-55C for 1 hour to yield 0.9 g of crystalline <strong>[202409-33-4]etoricoxib</strong> sulfamate (Purity by HPLC: 99.69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In ethyl acetate; isopropyl alcohol; at 25 - 30℃;pH 1; | Crude <strong>[202409-33-4]etoricoxib</strong> (10 g) was dissolved in ethyl acetate (40 ml) at 25-30C, followed by adjusting the pH to 1.0 with 18% isopropanolic HC1 (5 ml). The resulting mass was stirred for 1-2 hours and the resulting mass was filtered, washed with ethyl acetate (10 ml) and then dried at 50-55C for 1 hour to yield 10 g of <strong>[202409-33-4]etoricoxib</strong> hydrochloride salt (Purity by HPLC: 88.58%). | |
With hydrogenchloride; In methanol; water;Cooling with ice; | Etoxioxetine (358 mg, 1 mmol) and hydrochloric acid (0.5 mmol) were placed in an ice bathAdd to a 50ml Erlenmeyer flaskAdd 20ml of methanol, add in batches,When the solution has a slight turbidity, stop adding, and stir for hours.It was placed in an explosion-proof refrigerator at room temperature of 10 degrees and slowly deposited to obtain a product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetone; toluene; at 20 - 55℃; | Toluene (5 ml) and <strong>[202409-33-4]etoricoxib</strong> (1 g) were taken into a reaction flask, the mixture was heated at 50-55C, followed by the addition of benzenesulfonic acid (0.50 g). Acetone (2ml) was added to the resulting mass, the reaction mass was cooled to 20-25C and maintained for 2 hours. The solid obtained was filtered, washed with toluene (3 ml) and then dried at 50-55C for 1 hour to yield 1.08 g of crystalline <strong>[202409-33-4]etoricoxib</strong> benzenesulfonate salt (Purity by HPLC: 99.64%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; In water;pH 8.5 - 9; | Pure etoricoxib salicylate salt (10 g, HPLC purity: 99.86%>) was suspended in water (20 ml), followed by adjusting the pH to 8.5 to 9.0 with aqueous ammonia (20 ml) and extracting the product with ethyl acetate (3 x 40 ml). The resulting organic layer was charcolized (Darco G60) at 25-35C, filtered through a hyflo bed and washed with ethyl acetate (20 ml) at 25- 35C. Ethyl acetate was distilled off completely from the resulting filtrate at 45-50C under reduced pressure, followed by stripping off the ester solvent with isopropanol and then dissolving the resulting residual mass in isopropanol (120 ml) at 50-60C. The reaction mixture was cooled to 0-5C and stirred for 2 hours. The resulting product was filtered and washed with isopropanol (20 ml). The resulting solid was dried under vacuum at 50-55C to give 6 g of pure etoricoxib (HPLC Purity: 99.96%>). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium molybdate; sulfuric acid; dihydrogen peroxide; In methanol; at 55℃; for 0.25h; | To a solution of 5-chloro-3-(4-methylthiophenyl)-6'-methyl-[2,3']bipyridine (4) (50g, 0.15mol) and sulfuric acid (6g, 0.061mol) in methanol (300mL) was added sodium molybdate (1.2g, 0.004mol). The solution was heated to 55 C, and was added hydrogen peroxide (40mL, 30%). The reaction mixture was kept stirring for 15 min and NaHS03(60mL, 30%) was added. The reaction mixture then was cooled to room temperature, organic solvent was removed under reduced pressure and water (lOOmL) was added. The aqueous solution was washed with ethyl acetate (50mL) 2 times, treated with charcoal and filtered. The solution was basified by NaOH solution (20%) and the precipitate was collected, washed with water (50mL). The solid was recrystallized with aqueous ethanol solution and dried in vacuum to give an off-white solid (51.6g, 94%) of compound of formula (1), m.p. 135.5-135.9 C; 'H NMR (400MHz, CDC13), delta (ppm): : 8.72 (d, J= 2.0 Hz, 1H), 8.38 (d, J= 2.0 Hz), 7.91 (dd, J= 1.6, 6.4 Hz, 2H), 7.74 (d, J= 2.4 Hz, 1H), 7.56 (dd, J= 2.4, 8.0 Hz, 1H), 7.41 (dd, J= 2.0, 6.8 Hz, 2H), 7.09 (d, J= 8.4 Hz, 1H), 3.09 (s, 3H), 2.54 (s, 3H).13C NMR (400MHz, CDC13), delta (ppm): : 158.6, 152.4, 149.8, 148.4, 143.8, 140.3, 137.9, 137.4, 135.3, 131.3, 131.2, 130.4, 127.9, 122.8, 44.5, 24.2; MS: 359 (M+l). |
Example-21Preparation of 5-Chloro-3-(4-methylsulphonyl) phenyl-2-(2-methyl-5-pyridyl) pyridine (I)Compound of formula (IV) viz. 5-chloro-3-(4-methylthio) pheny]-2-(2-methyl-5-pyridyl)- pyridine (10 gms) was dissolved in dichloromethane (100 ml) and stirred at 25-28C . Sulphuric acid (0.94 gms) dissolved in water (0.5 ml) was added slowly to the above solution at 10-15C. A solution of sodium tungstate (0.17 gms) in water (1.5 ml) was then added gradually to it, followed by further addition of methyl-tri-n-octylaminonium chloride (0.25 gms) and dichloromethane (2 ml). The reaction mass was then subjected to oxidation by gradual addition of 50% hydrogen peroxide solution (8.12 gms) in water (2 ml), while maintaining the reaction temperature at 12-14C over a period of approximately 1.5 to 2.0 hrs. The reaction temperature was gradually raised to 28-30C and maintained for several hours while monitoring by TLC till reaction completion. Reaction mass was added with water (50 ml), and 10% sodium bicarbonate solution to maintain pH at 6.95-7.15. Dichloromethane layer containing product was separated and aqueous mass was extracted twice with dichloromethane (25 ml). Dichloromethane layers were mixed, washed twice with water (20 ml), dried over anhydrous sodium sulphate and treated with active carbon (0.8 gms). Filtered product solution was concentrated by distillation to obtained product residue. Solvent traces were removed by vacuum application and isopropanol (30 ml) was added. The mass was cooled to (-)2-2C for a period of 2 hrs. Product was isolated by filtration, washed with cooled IPA (3 ml) followed by drying at 60-70C (yield 7.5 gms,m.p. 131 -134C HPLC purity = 96.89%, light creamish colored powder). | ||
Example-19 Preparation of 5-Chloro-3-(4-methylsulphonyl)phenyl-2-(2-methyl-5-pyridyl)pyridine (I) Compound of formula (IV) viz. 5-chloro-3-(4-methylthio)phenyl-2-(2-methyl-5-pyridyl)-pyridine (10 gms) was dissolved in dichloromethane (100 ml) and stirred at 25-28 C. Sulphuric acid (0.94 gms) dissolved in water (0.5 ml) was added slowly to the above solution at 10-15 C. A solution of sodium tungstate (0.17 gms) in water (1.5 ml) was then added gradually to it, followed by further addition of methyl-tri-n-octylammonium chloride (0.25 gms) and dichloromethane (2 ml). The reaction mass was then subjected to oxidation by gradual addition of 50% hydrogen peroxide solution (6.87 gms) in water (2 ml), while maintaining the reaction temperature at 8-10 C. over a period of approximately 1.5 to 2.0 hrs. The reaction temperature was gradually raised to 28-30 C. and maintained for several hours while monitoring by TLC till reaction completion. Reaction mass was added with water (50 ml), and 10% sodium bicarbonate solution to maintain pH at 6.8-7.0. Dichloromethane layer containing product was separated and aqueous mass was extracted twice with dichloromethane (25 ml). Dichloromethane layers were mixed, washed twice with water (20 ml), dried over anhydrous sodium sulphate and treated with active carbon (0.8 gms). Filtered product solution was concentrated by distillation to obtained product residue. Solvent traces were removed by vacuum application and isopropanol (30 ml) was added. The mass was cooled to (-)2-2 C. for a period of 2 hrs. Product was isolated by filtration, washed with cooled IPA (3 ml) followed by drying at 60-70 C. (yield 7.2 gms, m.p. 129-131 C. HPLC purity=97.14%, light creamish colored powder). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Etoricoxib-PTSA salt obtained above (28 gm) was added with water (250 ml) and stirred at ambient temperature for 15-20 minutes. Gradually 10% sodium bicarbonate solution was added till pH was around 7.90 to 8.10, followed by toluene (50 ml). The reaction mixture was heated to 50-55C, stirred for 10 minutes and allowed to stand. Toluene layer containing product was separated and the aqueous layer was extracted twice with toluene (80 ml) in a similar manner combined toluene layer was washed with water (100 ml), treated with active carbon (2.5 gms), dried over anhydrous sodium sulphate, filtered and concentrated at 60-65C under reduced pressure to obtain a residue. Isopropanol (94 ml) containing 4% water was added to the residue and it was heated to 55-65C to dissolve. The solution was slowly cooled to ambient temperature and then to 5-10 for 1.5 hrs. Product mass was filtered, washed with cold isopropanol (10 ml), and dried at 60-65C till constant weight (yield 1 1 gms,m.p. 135-137C, HPLC purity = 99.23%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In isopropyl alcohol; at 65℃; | 250mg 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridinyl and 102 mg of adipic acid were dissolved in 15ml of isopropanol at 65C to give a slightly yellow solution. The solution was cooled to room temperature then allowed to evaporate to yield the desired adipic acid salt as a white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetone; at 40℃; | 1.0g of 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridinyl and 0.5g of saccharin were dissolved in 20ml of acetone at 40 C. The solution was cooled to 5 C to crystallize the desired saccharin salt. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water; sodium hydroxide; at 25 - 35℃; | To a stirred solution of sodium hydroxide (20.20 g) in water (250 mL), etoricoxib hydrochloride (50 g) was added at a temperature of 25C to 35C. The reaction mixture was stirred and extracted with methylene dichloride (250 mL). The separated organic layer was filtered through a hyflow bed and distilled out to give a residue. Isopropyl acetate (100 mL) was added to the residue and heated at 50-55C. The reaction mixture was cooled to 0-10C and solid was filtered. The solid was dried to obtain the crystalline Form-I of etoricoxib. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70 mg | With acetic anhydride; zinc; In formic acid; at 15 - 20℃; for 1h; | To a mixture of 5-chloro-6?-methyl-3- (4- (methylsulfonyl)phenyl)-2,3?-bipyridin-6-yl 4- methylbenzenesulfonate (250 mg, 0.473 mmol) and acetic anhydride (0.2 ml) in formic acid(10 ml), stirred at 15C (temperature of water bath), zinc (500 mg) was added. The mixture was stirred at that temperature for 5 mm, and further stirred at -20C for 1 hour. Then, 20 ml of ethyl acetate was added. The mixture was stirred for 5 mm, and the supernatant was decanted. The residue was washed again with ethyl acetate (20 ml), and the solvent was decanted. The combined organic layers were concentrated in vacuo to give an oil. The oil wasdissolved in MeOH (10 ml) and water (lml), and treated with 100mg NaOH at 50C for 30 mm. The mixture was concentrated in vacuo.DCM (15 ml) and water (15 ml) were added to the concentrated product, and the mixture was stirred for 10 mm. The separated DCM layer was dried, and concentrated to give the crude product as a solid (70 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With bis(eta3-allyl-mu-chloropalladium(II)); 5-(di(adamantan-1-yl)phosphino)-1?,3?,5?-triphenyl-1?H-1,4?-bipyrazole; potassium phenolate; In 1,4-dioxane; at 100℃; for 6h;Sealed tube; Glovebox; | The combination of high functional group compatibility and the tolerance of basicfunctional groups should allow this reaction to occur with a wide range of medicinally relevantcompounds. For example, the coupling of <strong>[202409-33-4]Etoricoxib</strong> with trifluoroaniline occurred with low loadings of the catalyst without undergoing side reactions. This reaction is shown below: Compound 30 was obtained as a white solid using the stated general procedure with the catalyst loading specified below. It was purified by column chromatography, eluting with 1.0% triethylamine, 10% methanol in dichloromethane. The catalyst loading and isolated yield for aryl chloride was as follows: 0.500 mol% catalyst, 94% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.7% | With hydrogenchloride; In isopropyl alcohol; at 10 - 20℃; for 2h; | Add 400 mL isopropanol solution to 259 g crude <strong>[202409-33-4]etoricoxib</strong> (HPLC purity 88.1%). Under stirring, dropwise add 170 mL of 4mol/L hydrochloric acid isopropanol solution at 15C. Stir mixture for 2h at 10-20C to precipitate out hydrochloride. Filter. Wash filter cake twice using isopropanol 100 mL. vacuum dry at -0.08MPa~0.01MPa, 60C for 16h to obtain 233 g yellow solid <strong>[202409-33-4]etoricoxib</strong> hydrochloride. Yield 91.7%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.5% | With sodium hydrogencarbonate; In dichloromethane; water; at 10 - 20℃; for 0.5h;Large scale; | Dichloromethane (4.5 L) was added at 10 to 20 & lt; 0 & gt; C with etjucoxime hydrochloride (2.25 kg)A 10% aqueous solution of sodium hydrogencarbonate (10 Kg)(The mass concentration refers to the mass of sodium bicarbonate as a percentage of the total mass of the aqueous sodium bicarbonate solution).Stir for 30 minutes,Liquid separationThe organic phase was washed twice with saturated sodium chloride (6 L)Dispensing.The organic phase was added to n-heptane (4.5 L) and dried over anhydrous sodium sulfate (1 kg)Filtered with silica gel (200 to 300 mesh; 2 kg)The filter cake was mixed with 1: 1 mixture of methylene chloride and n-heptane (1 L)And dichloromethane (1 L) rinsed twice,Combined mother liquor,-0.08MPa ~ 0.01MPa, 15 ~ 40 under reduced pressure to dry.The residue was dissolved by adding 4 L of isopropanol and heating to 60 C to 70 C.The solution was cooled to 17 to 22 C with stirring to precipitate a solid,filter;The filter cake was rinsed with isopropanol (1 L), n-heptane (1 L)50 C vacuum drying for 18 hours to get 1.95 kg of ethers.Yield 96.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); cesium fluoride; In 1,4-dioxane; for 20h;Inert atmosphere; Reflux; | In a 500 mL single-necked flask,Bromo-5-chloro-3- (4- (methylsulfonyl) phenyl) pyridine (17.4 g, 0.050 mol)Was dissolved in 1,4-dioxane (100 mL)Cesium fluoride (15.2 g, 0.100 mol) was added successively,Cuprous iodide (1.0 g, 0.005 mol)2-methyl-5-pyridineboronic acid (20.6 g, 0.150 mol)And tetrakis (triphenylphosphine) palladium (0.6 g, 0.001 mol)The reaction was refluxed under N2 for 20 h. Reaction finished,The reaction was quenched with water, cooled, filtered, extracted with ethyl acetate (100 mL x 3)The extract was washed with saturated sodium chloride solution (50 mL x 1), dried over anhydrous sodium sulfate,The solvent was distilled off under reduced pressure, the residue was beaten with a small amount of isopropyl ether,The residue was dried to give 29.7 g of the desired product 5-chloro-6'-methyl-3- (4- (methylsulfonyl) phenyl) -2,3'-bipyridine in a yield of 55%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | To a solution of 5-chloro-6?-methyl-3-(4-(methylsulfonyl)phenyl)-2,3?-bipyridine (384 mg, 1.07 mmol) in CH2Cl2 (11 mL) at -78 C was added Tf2O (180 muL, 1.07 mmol) dropwise over 5 min. The reaction was stirred for 30 min before PPh3 (309 mg, 1.18 mmol) and NaOAc (88 mg, 1.07 mmol) were added in one portion. The reaction was subjected to three rapid cycles of vacuum/nitrogen backfill and stirred for a further 30 min at -78 C. DBU (160 muL, 1.07 mmol was added dropwise, the cooling bath was removed and the reaction was allowed to warm to room temperature while stirring (approximately 15 min). The reaction mixture was quenched with H2O (30 mL) and the mixture transferred to a separatory funnel. The mixture was diluted with CH2Cl2 and the resulting organic layer was washed three times with H2O. The organic layer was dried (MgSO4), filtered and concentrated to approximately 10 mL. The concentrated solution was added to an excess of Et2O (- 20 C) and then placed in a -20 C refrigerator 1 h. The resulting solid was filtered on a frit and dried in vacuo to provide the title compound 1s (603 mg, 0.78 mmol, 73% yield) as a white solid. mp 157-163 C; IR numax/cm-1 (film): 3062, 1709, 1577, 1542, 1485, 1436, 1311, 1261, 1223, 1150, 1101, 1030, 921, 888, 715, 690, 636; 1H NMR (400 MHz, CDCl3) delta: 8.28 (1H, d, J = 7.1 Hz, H1), 8.10 (2H, d, J = 8.2 Hz, H6), 7.86-7.62 (16H, m, H4, H7, H8, and H9), 7.51-7.45 (3H, m, H3 and H5), 7.20 (1H, d, J = 16.5 Hz, H2), 3.14 (3H, s, H10), 2.54 (3H, s, H11); 13C NMR (100 MHz, CDCl3) delta: 160.84 (d, J = 11.2 Hz), 152.42 (d, J = 7.3 Hz), 147.53 (d, J = 2.2 Hz), 146.09, 141.53, 141.02, 138.92, 135.62, 134.84 (d, J = 2.9 Hz), 134.17 (d, J = 10.0 Hz), 133.29 (d, J = 3.6 Hz), 132.10, 130.76 (d, J = 10.2 Hz), 130.03 (d, J = 13.1 Hz), 129.86, 128.55, 128.19 (d, J = 86.2 Hz), 120.77 (q, J = 321.1 Hz), 119.34 (d, J = 91.8 Hz), 43.96, 24.55; 19F NMR (365 MHz, CDCl3) delta: -78.14; 31P NMR (162 MHz, CDCl3) delta: 25.54; m/z LRMS (ESI + APCI) found [M-OTf]+ 619.2, C36H29N2O2PS+ requires 619.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 20℃; for 0.0833333h;Sonication; | At room temperature, accurately weighed etanercept raw material (359mg, 1mmol)Was added to a 50 ml beaker, and phthalic acid (166 mg, 1 mmol)Under the ultrasound state anhydrous methanol was added dropwise until just completely dissolved, continue ultrasound 5min, filter paper filtration.The filtrate was transferred to a 50ml beaker. The 50ml beaker was placed in a large beaker containing purified water and the crystals were evaporated in vacuo (-0.05MP) at room temperature. About 72-96h after a large number of transparent crystal precipitation, filtration, cold methanol washing cake, that is, the desired salt. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; water; at 50 - 130℃; for 2h; | The <strong>[202409-33-4]etoricoxib</strong> 359mg was put into a 50ml methanol,2ml purified water in a single-mouth flaskPlaced in a 50C oil bathThen add 217mg of p-nitrobenzoic acid,Stir and dissolve,Pour the reaction solution into a small high pressure reactor.Then place it in an oven at 130 degrees Celsius.Stay for 2 hours,So <strong>[202409-33-4]etoricoxib</strong> and after sufficient reaction of p-nitrobenzoic acid,Let cool at room temperature.Pour the reaction solution into a 100ml single-mouth bottle.Under ice bath conditions,Vacuum evaporation (vacuum -0.03MPa),After 4h,A lot of transparent crystals,Precipitation,filter,The filter cake is washed with cold methanol.The resulting crystals are the target salt crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60.7% | With potassium tert-butylate; In tetrahydrofuran; for 4h;Reflux; | 2.88 g (8.0 mmol) of <strong>[202409-33-4]etoricoxib</strong>, 1.81 g (12.0 mmol) of methyl 6-methylnicotinate, 1.35 g(12.0 mmol) of potassium t-butoxide and 25 ml of tetrahydrofuran were mixed and heated to reflux for 4 h.After the TLC detection reaction was completed,30 ml of water, 35 ml of dichloromethanewas slowlyadded, and the liquid phase was separated, and the aqueous phase was extracted with dichloromethane (35 ml × 2), dichloromethane was combined,washed twicewith saturated brine, and the organic phase was separated. The organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure.Purification by column chromatography gave 2.32 g of a white solid. That is, Compound A, the yield was 60.7 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
for 0.5h;Cooling with ice; | Under ice bath, <strong>[202409-33-4]etoricoxib</strong> (358 mg, 1 mmol) and p-toluenesulfonic acid (0.8 mmol) were added to a 50 ml Erlenmeyer flask, and 20 ml of methanol was added in portions. After stirring for half an hour, the solution was slightly turbid and stopped stirring. , placed in an explosion-proof refrigerator at 10 C, slowly precipitated, filtered to remove excess solvent, washed, vacuum dried to obtain the product.Example 2 Preparation of Etoxoxib to form a salt with p-toluenesulfonic acid |
Tags: 202409-33-4 synthesis path| 202409-33-4 SDS| 202409-33-4 COA| 202409-33-4 purity| 202409-33-4 application| 202409-33-4 NMR| 202409-33-4 COA| 202409-33-4 structure
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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 |
Sorry,this product has been discontinued.
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