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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Succinic anhydride is a cyclic anhydride and a nonclaevable ADC linker extracted from patent WO2009064913A1. Succinic anhydride can react with compound 4 of the patent to link the prodrug to an amine or hydroxy 1 group of a targeting polypeptide.
Synonyms: Succinyl Oxide; SA
4.5
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CAS No. : | 108-30-5 |
Formula : | C4H4O3 |
M.W : | 100.07 |
SMILES Code : | O=C(CC1)OC1=O |
Synonyms : |
Succinyl Oxide; SA
|
MDL No. : | MFCD00005525 |
InChI Key : | RINCXYDBBGOEEQ-UHFFFAOYSA-N |
Pubchem ID : | 7922 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H314-H317-H334 |
Precautionary Statements: | P501-P272-P260-P270-P264-P280-P284-P342+P311-P362+P364-P303+P361+P353-P333+P313-P301+P330+P331-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
86.4% | With aluminum (III) chloride In dichloromethane at 33 - 37℃; for 6 h; | 15.8 g of 1-methoxynaphthalene and 10.0 g of succinic anhydride were dissolved in 120 mL of dichloromethane,Stir,Cooling to 1 ~ 3 ° C,Divided into three batches of anhydrous aluminum trichloride 15.0 grams,The addition process takes about 20 minutes,The solution was then heated to 35 ± 2 ° C,Insulation reaction 6 hours (5.5 ~ 6.5 hours range),After the reaction is complete,The reaction solution was poured into an ice-water mixture (200 g of ice and 300 g of water) for 30 minutes,Standing, analysiscrystal,Filter,The filtrate was heated and distilled to recover dichloromethane,The cake is the crude of the ketone ketone;And then the crude ketoprofen water as a solvent by 2-3 times recrystallization,Activated carbon decolorization,Demon ketone boutique.The mass of the present product of the chamballone was 22.3 g,Melting point of 176 ~ 179 ° C,The yield was 86.4percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In toluene; at 20℃; for 40h;Dean-Stark; Reflux; | To a solution of succinic anhydride (100 g, 1000 mmol) in toluene (3000 mL) was added benzylamine (107 g, 1000 mmol). The solution was stirred at room temperature for 24 h, then heated at reflux with a Dean-Stark apparatus for 16 hours. The mixture was then concentrated under reduced pressure to give l-benzylpyrrolidine-2,5-dione (170 g, 900 mmol, 90% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | In N,N-dimethyl-formamide; at 20℃; for 18h; | Compound 4 (1 g; 0.88 mmol; 1 eq.) is dissolved in 20 ml of anhydrous DMF under an inert atmosphere, in a clean and dry 100 ml round-bottomed flask. Succinic anhydride (0.135 g; 1.34 mmol; 1.5 eq.) dissolved in 6 ml of anhydrous DMF is added. The reaction medium is left under an inert atmosphere for 18 hours at ambient temperature. The reaction is stopped with 120 muL of water and the solution is then precipitated from 200 ml of acetone. The solid obtained is filtered off and then dried in a desiccator. The solid is taken up in a minimum of water, the insoluble material is filtered off and the filtrate is lyophilized. Compound 5 is obtained with a 55percent yield. TLC: Rf=0.6 eluent: DMF/BuOH/H2O 1/2/1 (v/v/v) M.p.: 160° C. (decomposition) 1H NMR pyridine-d5 delta (ppm): 8.75 (s, 1H, NH-CD); 7.9-7.6 (14OH); 5.8-5.55 (m, 7H, H1-CD); 4.95-3.95 (m, H3-CD/H6-CD/H6'-CD/H5-CD/H4-CD/H2-CD); 3 (m, 4H, Hb/Hc) ESI-MS+: m/z measured at 1234.5 [M+H]+, calculated at 1234.4 for C46H76NO37 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15 g (0.902 mole) of <strong>[18979-61-8]rucinol</strong> was dissolved in pyridine solvent under atmosphere of nitrogen gas and 27.1 g (0.27 mole) of succinic anhydride was added to the solution. After then, the solution was subject to a reaction at room temperature for 24 hours under a state that the light was blocked. After the completion of the reaction, pyridine was adjusted to pH 2 by adding hydrochloric acid and thus converted into a salt form, and chloroform and water were added to extract and remove it. Similarly, an excessive succinic anhydride was also extracted and removed with the water layer. 4.06 g (0.011 mole) of <strong>[18979-61-8]rucinol</strong>-carboxyl acid obtained as above was dissolved in dichloromethane solvent under atmosphere of nitrogen gas and carboxyl group was activated by using 3.09 ml (0.022 mole) of triethylamine and 2.11 g (0. 011 mole) of p- toluenesulfonylchloride. After that, phytosphingosine, sphinganine or sphingadiene 7.75 g (0.024 mole) was slowly added to the solution and then was subject to a reaction for 24 hours while warming. After the completion of the reaction, the reaction was stopped by extracting with distilled water, and refined with an adsorption-chromatography by silica gel, so that compounds of the above formulas 1 to 3 were obtained. The succinate, which was introduced in <strong>[18979-61-8]rucinol</strong> by reacting with succinic anhydride, was confirmed with 1H NMR (6 = 2.6 ppm, t, 4H), and finally methylene of sphingolipid (8 = 1. 2 ppm, m, 48H and 8 = 0.9 ppm, t, 6H) and benzene group of <strong>[18979-61-8]rucinol</strong> (8 = 6.9 ppm, 6.35 ppm, d, t, 5H) were confirmed. Accordingly, it was confirmed that the derivative having <strong>[18979-61-8]rucinol</strong> and sphingolipid coupled was synthesized. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.670 g (86%) | With sodium acetate; In water; acetic anhydride; benzene; | EXAMPLE 47 STR151 2-Bromo-6-(N-succinimido)-naphthalene (29) A solution of <strong>[7499-66-3]2-amino-6-bromonaphthalene</strong> (0.565 g, 2.54 mmol) and succinic anhydride (0.508 g, 5.08 mmol) in 13 mL of benzene was refluxed for 1.5 hours. The resulting precipitate was isolated by filtration, washing with additional benzene. After drying in vacuo, 0.780 g of a solid was obtained which was dissolved in 12 mL of acetic anhydride along with sodium acetate (0.595 g, 7.26 mmol) and refluxed for 3 hours. After cooling to room temperature, the reaction mixture was quenched with 3 mL of water and was evaporated to dryness under high vacuum. Purification by flash chromatography through 150 g of silica gel (1:4 EtOAc/CH2 Cl2) yielded 0.670 g (86percent) of the title compound as a white solid. 1 H-NMR (300 MHz, CDCl3): delta 2.95 (bs, 4H), 7.41 (dd, J=8.8, 1.9 Hz, 1H), 7.59 (dd, J=8.8, 1.7 Hz, 1H), 7.73 (d, J=8.8 Hz, 1H), 7.79 (s, 1H), 7.84 (d, J=8.8 Hz, 1H), 8.04 ppm (s, 1H). FAB-MS: m/e=504,506 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 48h; | [00869] Specifically, beta-estradiol 17-acetate (1) and a 10-fold excess of succinic anhydride (2) were stirred together in DMF with 5 DIEA and DMAP for 48 hours at room temperature. After 48 hours, the reaction solvent was evaporated in vacuo and the product (3) was re-suspended in ethyl acetate. The reaction product (3) was washed with aqueous HC1 (0.0 IN) two times followed by a single wash with water. The ethyl acetate was evaporated in vacuo and the product (3) was re-suspended in a mixture of MeOH/acetonitrile/water. The estrogen derivative product (3) was purified by reverse-phase HPLC. Lyophilized product (3) and the resin-bound peptide were mixed in HOBt/DIC/NMP for 4 hours, filtered, treated with TFA, and cleaved from the resin by HF treatment. The peptide-estrogen conjugate was purified using reverse-phase HPLC and characterized by ESI mass spectrometry. | |
With dmap; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 48h; | Specifically, 3-estradiol 17-acetate (1) and a 10-fold excess of succinic anhydride (2) were stirred together in DMF with5percent DIEA and DMAP for 48 hours at room temperature. After48 hours, the reaction solvent was evaporated in vacuo and the product (3) was re-suspended in ethyl acetate. The reaction product (3) was washed with aqueous HC1 (0.0 iN) two times followed by a single wash with water. The ethyl acetate wasevaporated in vacuo and the product (3) was re-suspended ina mixture of MeOH/acetonitrile/watet The estrogen derivative product (3) was purified by reverse-phase HPLC. Lyophilized product (3) and the resin-bound peptide were mixed in H013t/DIC/NMP for 4 hours, filtered, treated with TFA,and cleaved from the resin by HF treatment. The peptideestrogen conjugate was purified using reverse-phase HPLC and characterized by ESI mass spectrometry. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In tetrahydrofuran; at 110℃; for 1.5h;Microwave irradiation; | 4-((2-cyanobenzo[d]thiazol-6-yl)amino)-4-oxobutanoic acid (1). 6- aminobenzo[d]thiazole-2-carbonitrile (2.0 g, 11.4 mmol), succinic anhydride (1.3 g, 13 mmol) and THF (15 mL) were placed in a 25 mL vessel and heated in a microwave synthesizer for 90 minutes at 110°C. Upon cooling, the reaction mixture was triturated with Et20 and filtered, dried and evaporated to give 3.1 g of the product as a light yellow solid (99percent). IH-NMR (d6-DMSO, 300 MHz): delta 12.15 (s, 1H), 10.45 (s, 1H), 8.71 (s, 1H), 8.16 (d, 1H, J = 8.2 Hz), 7.70 (d, 1H, J= 8.2 Hz), 2.62 (m, 2H), 2.55 (m, 2H). ESI-MS: Calc. C12H10N3O3S +: m/z 276.3; found m/z 276. tert-butyl (18-((2-cyanobenzo [d] thiazol-6-yl)amino)- 15,18-dioxo-4,7, 10-trioxa-14- azaoctadecyl)carbamate (2). Compound 1 (4.93g, 17.9 mmol), tert-butyl (3-(2-(2-(3- aminopropoxy)ethoxy)ethoxy)propyl)carbamate (7.40 g, 23.1 mmol) and DCM:DMF (10: 1, 100 mL) were stirred together in a 250 mL round bottomed flask at room temperature. ED AC (4.0 g, 20.9 mmol) was added and the reaction was stirred for 20h. The solvent was evaporated and purified by normal phase chromatography with DCM/MeOH as solvent to give 6.62 g of a white solid (64percent). IH-NMR (d3-ACN, 300 MHz): delta 9.21 (s, NH), 8.62 (d, 1H, J = 2.0 Hz), 8.09 (d, 1H, J = 8.4 Hz), 7.63 (d, 1H, J = 8.4 Hz), 6.65 (bs, NH), 5.40 (bs, NH), 3.5 (m, 12 H), 3.28 (m, 2H), 3.06 (m, 2H), 2.65 (m, 2H), 2.51 (m, 2H), 2.70 (m, 4H), 1.40 (s, 9H). ESI-MS: Calc. C27H40N5O7S +: m/z 578.7; found m/z 578.4. Nl-(3-(2-(2-(3-aminopropoxy)ethoxy)ethoxy)propyl)-N4-(2-cyanobenzo[d]thiazol-6- yl)succinamide hydrochloride (3). Compound 2 (6.62 g, 11.5 mmol) was stirred in a 500 mL round bottomed flask with DCM (200 mL) and triisopropylsilane (1 mL). A 4.0 M solution of HCl in dioxane (30 mL, 120 mmol) was added and stirred at room temperature for 3h. The solvent was evaporated to give 6.4 g of a yellow hygroscopic solid (98percent). 1H-NMR (d6-DMSO, 300 MHz): delta 10.62 (s, 1H), 8.74 (d, 1H, J = 2.0 Hz), 8.15 (d, 1H, J = 8.4 Hz), 7.77 (d, 1H, J = 8.4 Hz), 3.4 (m, 16 H), 3.28 (m, 2H), 3.08 (m, 2H), 2.80(m, 2H), 2.61 (m, 2H), 2.41 (m, 2H), 1.80, (m, 2H), 1.60 (m, 2H). ESI-MS: Calc. C22H32N505S +: m/z 478.59; found m/z 478.2. Immobilized cyanobenzothiazole-magnetic cellulose (4). Carboxymethyl magnetic cellulose (7.24g, 30-50 muiotaeta, Iontosorb MG CM) was taken up in a 250 mL round bottomed flask with compound 3 (800 mg, 1.53 mmol) in DMF (100 mL). ED AC (387 mg, 2.01 mmol) was added, and the reaction was stirred for 20h at room temperature. The particles were filtered on a frit and rinsed first with DMF (200 mL) then 25percent EtOH (300 mL) and stored as a 50percent> suspension at 4°C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; for 2.5h;Reflux; | General procedure: A mixture of succinic anhydride (1.0 eq) and dry alcohol (1 eq) in toluene (4 mL) was heated at reflux 2.5 h. The toluene was removed under reduced pressure and the residue was taken up in water, and the solution was extracted with dichloromethane, dried (MgSO4), and evaporated to afford monoalkylsuccinic acid. A solution of monoalkyl succinic acid (1.2 eq) and thionyl chloride (1.4 eq) in benzene (5 mL) was refluxed for 3 h. Subsequently, the majority of the SOCl2 and benzene were removed by distillation. The mixture was cooled down to room temperature and dried under a vacuum to give a crude chlorocarbony-alkyl ester. A solution of chlorocarbonyl-alkyl ester in dichloromethane (5 mL) was added to a round flask containing 14 (1 eq) by cannula, and subsequently added pyridine (1.4 eq). The resulting solution was stirred at room temperature overnight, and quenched by adding water. The solution was extracted with ethyl acetate, dried (MgSO4), and evaporated to give a residue which was purified by column chromatography (Al2O3), eluting by ethyl acetate /hexane (1:15) to provide 25?43. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; for 3h; | [00171 ] Synthesis of compound 9. N-(2-hvdroxyethyl)-1 H-pyrrole-2-5-dione (141 mg, 1 .00 mmol) was dissolved in dichloromethane (1 mL), triethylamine (101 mg, 1 .00 mmol) was added, followed by succinic anhydride. After 3 hours, solvent was evaporated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[00243] 2-Hydroxyethyl maleimide (120 mg, 0.85 mmol, 2.00 equiv) was suspended in THF (4.0 mL) then A/-methyl morpholine (93 mu, 0.85 mmol, 2.0 equiv) was added followed by succinic anhydride (85 mg, 0.85 mmol, 2.0 equiv). The solution was stirred at room temperature for 16 hours, then N- methyl morpholine (93 mu, 0.85 mmol, 2.0 equiv) was added followed by isobutyl chloroformate (1 10 mu, 0.85 mmol, 2.0 equiv) and the solution was stirred at room temperature for 45 minutes. Water (10 mL) and ethyl acetate (10 mL) were added and the layers were separated. | ||
2-Hydroxyethyl maleimide (120 mg, 0.85 mmol, 2.00 equiv.) was suspended in THF (4.0 mL) then N-methyl morpholine (93 uL, 0.85 mmol, 2.0 equiv.) was added followed by succinic anhydride (85 mg, 0.85 mmol, 2.0 equiv.). The solution was stirred at room temperature for 16 hours, then N-methyl morpholine (93 uL, 0.85 mmol, 2.0 equiv.) was added followed by isobutyl chloroformate (110 uL, 0.85 mmol, 2.0 equiv.) and the solution was stirred at room temperature for 45 minutes. Water (10 mL) and ethyl acetate (10 mL) were added and the layers were separated. Solvent was then evaporated, then the activated ester was dissolved in DMF and hydroxy(2- methylethoxyacetoxy)oxalplatin(IV) (233 mg, 0.43 mmol, 1.0 equiv.) was added and solution was stirred sat 50 °C for 18 hours. Solvent was evaporated from this mixture and the crude product was purified on silica gel (0-8percent MeOH/DCM gradient) to afford the desired product with residual MeOH. The residue was dissolved in MeOH (2 mL) and the resulting solution was added to TBME (50 mL) to obtain a white precipitate (compound 13) that was filtered and dried under vacuum. Compound 13 was obtained as an off- white solid (131 mg, 40percent yield). HPLC/MS (method B): 3.41 minutes, M+H = 771 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With CBV780; at 140℃; for 0.5h;Microwave irradiation; | The same procedure as in Example 1 was repeated with varying reaction conditions (such as catalysts, starting materials, reaction temperature, reaction time and the like), to carry out reactions, and the analyses of the resulting products. The results of the yields of the respective products as measured by gas chromatography or nuclear magnetic resonance spectroscopy are shown in Table 1-ito Table 1-7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With triethylamine; In N,N-dimethyl acetamide; at 60℃; for 2h; | 2.1 g (10 mmol) of 9,10-dihydroxyanthracene, 2.5 g (25 mmol) of succinic anhydride and 15 g of N, N-dimethylacetamide were added to a three-necked flask equipped with a stirrer, To a yellow-green slurry, a solution of 2.0 g (20 mmol) of triethylamine in 4 g of N, N-dimethylacetamide was added dropwise. It became a slightly brown slurry. Subsequently, the mixture was heated at 60 ° C. for 2 hours to obtain a brown solution. After cooling to room temperature, it was poured into a 3percent sulfuric acid aqueous solution, and a large amount of ocher-colored precipitation occurred. The precipitate formed was suction filtered, washed with water and dried to obtain 2.7 g (6.5 mmol) of an ocher powder of 9,10-bis (2-carboxyethyl) carbonyloxyanthracene.Isolated yield to 9,10-dihydroxyanthraceneWas 65 molpercent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With acetic acid; at 20℃; for 2h; | To a stirred solution of 2-amino-4-methyl-benzamide (190 mg, 1.27 mmol) in AcOH (5 mL),succinic anhydride (151 mg, 1.52 mmol) was added at RT and stirred for 2 h (TLC indicatedcomplete consumption of starting material). The reaction mixture was diluted with water (20mL), solid was precipitated out, filtered and dried under vacuum to get the required 4-(2-carbamoyl-5-methyl-anilino)-4-oxo-butanoic acid (250 mg, 89percent) which was used for nextstep without further purification.1H NMR [300 MHz, DMSO-d6]: J 12.37 (brs, 1H), 11.88 (s, 1H), 8.33 (s, 1H), 8.20 (s, 1H),7.70 (d, J = 8.1 Hz, 1H), 7.64 (s, 1H), 6.91 (d, J = 7.8 Hz, 1H), 2.53-2.50 (m, 4H), 2.31 (s,3H).LCMS: m/z: 273.50 [M+Nat. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With acetic acid; at 20.0℃; for 4.0h; | To a stirred solution of <strong>[50608-99-6]3-aminopyridine-2-carboxamide</strong> (0.3 g, 2.19 mmol) in AcOH(3 mL), succinic anhydride (0.26 g, 2.63 mmol) was added at RT and stirred for 4 h (TLCindicated complete consumption of starting material). The reaction mixture was poured intoice cold water (5 mL) and stirred for 30 min during which solid precipitated out. The solidwas filtered, washed with water (10 mL), cold acetone (5 mL) and dried under high vacuumto provide 4-[(2-carbamoyl-3-pyridyl)amino]-4-oxo-butanoic acid (320 mg, 61 %) which wasused for the next step without any purification.LCMS: m/z: 238.41 [M+Ht |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; | Manual synthesis using FMOC solid phase synthesis strategy. Using FMOC-Gly-Wang resin (glycine bonding amount is0.698mmol/g) as starting material, 20percent hexahydropyridine/DMF as deprotecting reagent, N-methylmorpholine and HBTU as liveChemical reagent.The specific synthesis step of the AP2H polypeptide sequence is as follows: the weighed FMOC-Gly-Wang resin is loaded into the sand core funnel,DMF was swollen for 30 minutes and then washed three times with DMF. Add 20percent hexahydropyridine/DMF solution at a ratio of 30 mL/g resin, magneticAfter stirring for 5 minutes, the mixture was drained and repeated twice to remove the FMOC protecting group. Wash the resin with DMF six times, stirring for 1 minute each time, pumpingDry for 10 seconds. Dissolving a mixture of FMOC-AA-OH with HBTU and HOBt with 0.4 mol/L N-methylmorpholine/DMF solution, will liveThe amino acid solution after the addition is added to the resin, and after the magnetic stirring reaction for 2 hours, the Kaiser test is performed, and the resin is not blue-violet.The color indicates complete reaction, otherwise the reaction time is extended, or the coupling reaction is repeated once, and then the resin is washed six times with DMF. repeatThe above steps, in order to complete the extension of the polypeptide chain, complete the synthesis of the AP2H polypeptide sequence (IHGHHIISVG), and then remove the peptide amino group.End FMOC protecting group.After the AP2H polypeptide sequence is synthesized, the FMOC protecting group is removed, and a 3-fold molar amount of succinic anhydride is added, and the coupling is coupled.After the beam is washed, add 3 times the molar amount of FMOC-NH-NH2, HBTU and HOBt to react overnight, after the reaction is finished, remove the FMOC protection.Base, using freshly prepared lysate (95percent TFA, 2.5percent H2O, 2.5percent TIS, v/v/v) to AP2H-hydrazideThe product is cleaved from the resin, and the obtained crude product is purified by Shimadzu semi-preparative liquid chromatography, pure liquid chromatography and mass spectrometry. The spectrum was characterized. The results are shown in Figures 2 and 3. |
Tags: Succinic anhydride | Anhydrides | Ketones | Tetrahydrofurans | ADC Linker | Esters | Heterocyclic Building Blocks | Antibody-Drug Conjugate/ADC Related | Organic Building Blocks | ADC | 108-30-5
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P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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