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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.
1-Methylimidazole is an imidazole derivative used as an enzyme inhibitor or catalyst in organic synthesis and biological research.
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Modulating the Potency of BRD4 PROTACs at the Systems Level with Amine-Acid Coupling Reactions
McGrath, Andrew ; Huang, Haiyan ; Brazeau, Jean-Francois ; Zhang, Zirong ; Audu, Christopher O ; Vellore, Nadeem A , et al.
Abstract: Protein degradation using proteolysis targeting chimeras (PROTACs) represents a promising therapeutic strategy. PROTACs are heterobifunctional molecules that consist of a target-binding moiety and an E3 ligase binding moiety, connected by a linker. These fragments are frequently united via amide bonds. While straightforward to synthesize, amides may impart suboptimal drug properties to the overall molecule. From a systems level perspective, we envisioned that the potency of PROTACs could be modulated through selection of reaction conditions-wherein different catalysts produce distinct linkers from the same two building blocks. We present a suite of BRD4 PROTAC degraders prepared via four new amine−acid coupling reactions alongside the classic amide coupling. Our findings reveal that variations in reaction conditions affect the physicochemical properties of PROTACs, resulting in a spectrum of properties. Notably, several new PROTACs demonstrated enhanced BRD4 degradation efficacy compared to those employing amide linkers, emphasizing the potential of systems chemistry as a therapeutic optimization strategy.
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Surveying the scope of aromatic decarboxylations catalyzed by prenylated-flavin dependent enzymes
Anushree Mondal ; Pronay Roy ; Jaclyn Carrannatto ; Prathamesh M. Datar ; Daniel J. DiRocco ; Katherine Huntera and E. Neil G. Marsh
Abstract: The prenylated-flavin mononucleotide-dependent decarboxylases (also known as UbiD-like enzymes) are the most recently discovered family of decarboxylases. The modified flavin facilitates the decarboxylation of unsaturated carboxylic acids through a novel mechanism involving 1,3-dipolar cyclo-addition chemistry. UbiD-like enzymes have attracted considerable interest for biocatalysis applications due to their ability to catalyse (de)carboxylation reactions on a broad range of aromatic substrates at otherwise unreactive carbon centres. There are now ∼35[thin space (1/6-em)]000 protein sequences annotated as hypothetical UbiD-like enzymes. Sequence similarity network analyses of the UbiD protein family suggests that there are likely dozens of distinct decarboxylase enzymes represented within this family. Furthermore, many of the enzymes so far characterized can decarboxylate a broad range of substrates. Here we describe a strategy to identify potential substrates of UbiD-like enzymes based on detecting enzyme-catalysed solvent deuterium exchange into potential substrates. Using ferulic acid decarboxylase (FDC) as a model system, we tested a diverse range of aromatic and heterocyclic molecules for their ability to undergo enzyme-catalysed H/D exchange in deuterated buffer. We found that FDC catalyses H/D exchange, albeit at generally very low levels, into a wide range of small, aromatic molecules that have little resemblance to its physiological substrate. In contrast, the sub-set of aromatic carboxylic acids that are substrates for FDC-catalysed decarboxylation is much smaller. We discuss the implications of these findings for screening uncharacterized UbiD-like enzymes for novel (de)carboxylase activity.
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Purchased from AmBeed: 27916-43-4 ; 2438-05-3 ; 501-89-3 ; 42287-94-5 ; 776-79-4 ; 53473-36-2 ; 7251-61-8 ; 42287-97-8 ; 1621-91-6 ; 37718-11-9 ; 288-13-1 ; 86-73-7 ; 104-53-0 ; 2018-90-8 ; 87-66-1 ; 135-19-3 ; 1664-57-9 ; 289-80-5 ; 693-95-8 ; 55-22-1 ; 102-93-2 ; 1477-50-5 ; 1632-76-4 ; 4780-79-4 ; 16642-79-8 ; 3581-89-3 ; 501-97-3 ; 771-50-6 ; 98-98-6 ; 619-64-7 ; 100-51-6 ; 402-45-9 ; 59-67-6 ; 93-60-7 ; 273-53-0 ; 2084-13-1 ; 51-17-2 ; 2459-09-8 ; 2459-07-6 ; 95-16-9 ; 459-31-4 ; 90-05-1 ; 150-76-5 ; 103-25-3 ; 271-44-3 ; 6293-56-7 ; 2550-26-7 ; 288-32-4 ; 501-52-0 ; 2001-32-3 ; 1592-38-7 ; 95-15-8 ; 91-19-0 ; 1122-61-8 ; 3724-19-4 ; 20173-24-4 ; 118-31-0 ; 6125-24-2 ; 60-12-8 ; 90-15-3 ; 120-72-9 ; 822-36-6 ; 288-47-1 ; 288-42-6 ; 2038-57-5 ; 38628-51-2 ; 1929-29-9 ; 15009-91-3 ; 1505-50-6 ; 581-40-8 ; 616-47-7 ; 1571-33-1
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CAS No. : | 616-47-7 |
Formula : | C4H6N2 |
M.W : | 82.10 |
SMILES Code : | CN1C=CN=C1 |
MDL No. : | MFCD00005292 |
InChI Key : | MCTWTZJPVLRJOU-UHFFFAOYSA-N |
Pubchem ID : | 1390 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H227-H302-H311-H314 |
Precautionary Statements: | P210-P264-P270-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P361+P364-P370+P378-P403+P235-P405-P501 |
Class: | 8(6.1) |
UN#: | 2922 |
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 |
---|---|---|
73% | With triethylamine In acetonitrile at -20 - 30℃; for 12.5 h; Inert atmosphere | After replacing the inside of a 100 mL three-necked flask with an argon atmosphere, 22 mL of acetonitrile and 6.3 mL of methyl chloroformate were added and the mixture was cooled to -20 ° C. To this solution, a solution of 3.3 g of 1-methyl-1H-imidazole and 6.8 mL of triethylamine in 8 mL of acetonitrile was added in 30 minutes, followed by stirring at room temperature for 12 hours. After adding 50 mL of ethyl acetate to the reaction solution, insoluble matter was filtered off, and the residue was washed with 50 mL of ethyl acetate. The filtrate and the washing solution were combined, concentrated under reduced pressure,the concentrated residue was purified by column chromatography(Silica gel, hexane / ethyl acetate) to obtain 4.2 g (yield: 73percent) of methyl 1-methyl-1H-imidazole-2-carboxylate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5 h; Stage #2: at -78 - 20℃; for 2 h; |
General procedure: n-BuLi (1.67 M solution in hexane, 1.3 mL, 2.2 mmol) was added dropwise into a solution of p-bromoanisole (383 mg, 2.0 mmol) in THF (3 mL) at -78 °C for 30 min. Then, DMF (0.22 mL, 2.2 mmol) was added to the mixture and the obtained mixture was stirred at rt. After 2 h at the same temperature, THF was removed. Then, MeOH (3 mL) was added to the residue and the mixture was stirred at room temperature. After 30 min, I2 (1523 mg, 6 mmol) and K2CO3 (829 mg, 6 mmol) were added at 0 °C and the obtained mixture was stirred for 22 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3.x.20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide methyl 4-methoxy-1-benzoate in 82percent yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure methyl 4-methoxybenzoate as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With bromine; sodium acetate; In acetic acid; at 20℃; for 2.5h; | To a solution of N-methylimidazole (1.64 g, 19.97 mmol) and sodium acetate (25 g, 300 mmol) in acetic acid (180 mL) at room temperature was added bromine (9.6 g, 60.07 mmol) dropwise as a solution in 20 mL acetic acid. The resulting mixture was stirred for 2.5 h at room temperature. Acetic acid was removed in vacuo, the residue was suspended in 500 mL water and stirred at room temperature for 10 minutes. The resultant precipitate was filtered, washed with water and dried under high vacuum to give 2,4,5-tribromo-l-methyl- lH-imidazole (1.82 g, 29percent - some product remained in the mother liquor) as a light yellow powder. Used without further characterization. To a suspension of the tribromide (1.82 g, 5.71 mmol) in 45 mL water was added sodium sulfite (13 g, 103 mmol) and the resulting mixture was stirred at rapid reflux for 24 h. After cooling to room temperature, organics were extracted with ether (3 chi 75 mL), dried over magnesium sulfate, filtered and concentrated to give 1.61 g of a mixture of tri-, di- and monobromoimidazoles. This mixture was re-subjected to the reduction conditions (same quantity of sodium sulfite) using 15 mL of 3: 1 water/acetic acid as solvent and heating in a sealed vessel at 130 °C for 60 h. After cooling to room temperature, the pH of the reaction mixture was adjusted to 9-10 by addition of 2 N sodium hydroxide. Organics were extracted with ether (3 chi 50 mL), dried over magnesium sulfate, filtered and concentrated to give crude 4-bromo-l -methyl- lH-imidazole (571 mg, ca. 62percent). Used without further characterization.. 4-Butyl-l -methyl- lH-imidazole (95 mg, 22 percent) was synthesized as in Example 3.1 using 4-bromo-l -methyl- lH-imidazole (571 mg, ca. 3.53 mmol) in place of 5-bromo-2- formylfuran and propylboronic acid (372 mg, 4.24 mmol) in place of hexylboronic acid. Used without further characterization. To a solution of diisopropylamine (0.13 mL, 0.918 mmol) in 2 mL anhydrous tetrahydrofuran at - 0°C was added -butyllithium (0.34 mL, 2.5 M in hexanes) dropwise. The solution was stirred while warming to -20 °C over 20 minutes. After cooling to -78 °C, 4-butyl-l -methyl- lH-imidazole (95 mg, 0.765 mmol) was added dropwise as a solution in 2 mL anhydrous tetrahydrofuran. The resulting solution was stirred for 40 minutes at -78 °C. Dimethylformamide (0.24 mL, 3.06 mmol) was added and the solution stirred while warming to room temperature. The reaction mixture was poured into 15 mL of 1 N hydrochloric acid and stirred for 5 minutes. The pH of the reaction mixture was adjusted to 7-8 by careful addition of saturated sodium bicarbonate solution. Organics were extracted with dichloromethane (3 chi 20 mL), dried over magnesium sulfate, filtered and concentrated. The crude residue was subjected to chromatography on silica gel with gradient elution (5-50percent ethyl acetate in hexanes) to give l -methyl-4-propyl-lH-imidazole-2-carbaldehyde (9 mg, 8percent) as an off-white solid. Used without further characterization |
63.76 g | With N-Bromosuccinimide; In chloroform; at 20℃; for 1.5h; | 2-(2-Ethynyl-1 -methyl-1 H-imidazol-4-yl)-thiazole To a solution of compound N-methylimidazole (65.6 g, 0.8 mol) in CHCl3 (1 .5 L), N-bromosuccinimide (NBS; 476g,2.4 mol) was added in portion and then the mixture was stirred at roomtemperature for 1 .5 hour, filtered and concentrated, the residue was purifiedby column chromatography over silica gel (eluent: EA/PE 1/10) to afford 2,4,5-Tribromo-1 -methyl-1H-imidazole (63.76 g, 0.2 mol), which was dissolved in in dry THF (2L) andEtMgBr (220 ml_, 0.22 mol) was added slowly under N2 atmosphere at ambient temperature during 3 hourand stirred for another 2 hour. Then about 100ml_ water was added and filtered,concentrated and the residue was extracted with ethyl acetate, purified bycolumn chromatography over silica gel (eluent : EA/PE 1/10) to afford 2,4-dibromo-1 -methyl-1 H-imidazole (20 g, yield:41 .7percent). To a solution of 2,4-dibromo-1-methyl-1 H-imidazole (6 g, 25.6 mmol) in THF (26 ml_) was added Cul (0.2 g,1mmol), Et3N (12 ml_,86 mmol),Pd(dppf)CI2 (417 mg, 0.5 mmol),Ethynyl-trimethyl-silane (4.2 ml_,29.6 mmol), then the mixture was heated to40°C and stirred at this temperature for 40min. Then filtered, concentrated andpurified by column chromatography over silica gel (eluent: EA/PE 1/50), collectthe desire fraction and concentrated to give 4-Bromo-1-methyl-2-trimethylsilanylethynyl-1 H-imidazole (3.95 g, yield: 60percent). To a solution of 4-Bromo-1-methyl-2-trimethylsilanylethynyl-1 H-imidazole (5.14 g, 20 mmol) in toluene(100 ml_) , 2-Tributylstannanyl- thiazole (8.3 g, 22 mmol) was added followedwith Pd(PPh3) (1 .2 g, 1 mmol), then themixture was refluxed for 6 hour, when cooled, the mixture was filtered, thefiltrate was concentrated and purified by chromatography over silica gel (eluent :EA/PE 1/20 to 1/10) to afford 2-(1-Methyl-2-trimethylsilanylethynyl-1 H-imidazol-4-yl)-thiazole (2.5 g, yield:48percent). To the mixture of 2-(1 -Methyl -2-trimethylsilanylethynyl-1H-imidazol-4-yl)-thiazole in MeOH (50 ml_), Na2CO3 (1 .5 g, 18 mmol) was added quickly and stirred the mixture forabout one minutes, then filtered, concentrated and purified by column chromatographyover silica gel (eluent: EA PE 1/5) to afford 2-(2-Ethynyl-1 -methyl-1H-imidazol-4-yl)-thiazole (2 g, yield: 80percent). 1H NMR (CDCI3 400 MHz TMS):53.40 (s, 1 H), 3.80 (s, 3H), 7.27 (s, 1 H), 7.53 (s, 1 H), 7.26-7.27 (d, J=4.0Hz, 1 H). |
95 g | With bromine; sodium acetate; acetic acid; at 20℃; for 2.5h; | To a solution of Example 69a (82 g, 1.0 mol) and sodium acetate (125 g, 1.52 mol) in acetic acid (2.0 L) at room temperature was added bromine (480 g, 30 mmol) dropwise as a solution in 1.0L acetic acid. The resulting mixture was stirred for 2.5 h at room temperature. Acetic acid was removed in vacuo; the residue was suspended in 1.5L water and stirred at room temperature for 10 minutes. The resultant precipitate was filtered, washed with water and dried under high vacuum to give Example 69b (95.0 g, contained 30percent isomer) as light yellow powder. LCMS [M+H]+=319.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | 4.2-Second Variant:1-Methyl-imidazolium (2.74 g; 33.3 mmol) was mixed together with n-butanol (2.47 g; 33.3 mmol) in 40 mL of dichloromethane and, under stirring and cooling in an ice bath, anhydrous sulfonic trifluoromethane (9.40 g; 33.3 mmol) was added drop by drop. After finishing the addition to the mixture, it was stirred for 1 hour at room temperature, to which a saturated aqueous solution of sodium carbonate (3.54 g; 33.3 mmol) was added. The solution was stirred for 30 minutes at room temperature. The phases were separated, with an organic dry phase that uses anhydrous sodium carbonate. The solvent was evaporated under vacuum and gently heated (50 C.), producing the desired BMI.CF3SO3 (7.19 g; 75% yield), identical to the material obtained in experiment 1.2.4.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium tetrafluoroborate; at 70℃; for 336h; | In einen 1 I Schlenkkolben werden 126,0 g (1,53 mol) 1-Methylimidazol, 370,2 g (3,07 mol) Hexylchlorid und 251,8 g (2,30 mol) Natriumtetrafluoroborat gegeben und bei 70C ca. 2 Wochen geruehrt. Der entstandene weisse Feststoff wird ueber eine Schutzgasfritte abfiltriert und die sich gebildeten zwei Phasen voneinander mit Hilfe eines Scheidetrichters getrennt. Die untere gelbliche Phase wird ueber Nacht bei 60C im HV getrocknet. Man erhaelt 1-Hexyl-3-methylimidazoliumtetrafluoroborat in 91 %iger Ausbeute. Zum qualitativen Nachweis auf Chloridreste, werden ca. 1 ml des Produktes mit ca. 5 ml Wasser versetzt und mit 2 Tropfen konzentrierter Salpetersaeure angesaeuert. Zu dieser Loesung werden dann ca. 3-4 Tropfen Silbernitrat gegeben um etwaig vorhandenes Chlorid als Silberchlorid auszufaellen. Das Ausbleiben eines Niederschlags spricht fuer die komplette Abwesenheit von Chloridresten. 1H-NMR (300 MHz, CDCl3):delta=9.9 ppm (s,1H,Ha); delta=7.26 ppm (d,1H,Hc); delta=7.24 ppm (d,1H,Hd); delta=4.1 ppm (t,2H,He); delta=3.9 ppm (s,2H,Hb); delta=1.6 ppm (m,2H,Hf); delta=1.2 ppm (m,6H,Hg,h,i); delta=0.8 ppm (t,3H,HJ). 13C-NMR (75 MHz, CDCl3):delta=137 ppm (C1); delta=124-122 ppm (C3,C4); delta=48 ppm (C5); delta=35 ppm (C2); delta=29-24 ppm (C6-C8); delta=20 ppm (C9); delta=13 ppm (C10). 19F-NMR (281 MHz, CDCl3):delta= -151,3 ppm (d, 1J(BF)= 22 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In benzene; at 80℃; for 12h; | Example 1-(2); Synthesis of 1-ethylene Glycol Monomethyl Ether 3-methylimidazolium Methanesulfonate; 1-Methylimidazole (40 g) and ethylene glycol monomethyl ether methanesulfonate (90 g) were stirred at 80 C. for 12 hours in benzene in a 500 mL two-bulb flask equipped with a reflux condenser. After the reaction was completed, the product was washed several times with ethyl acetate or diethyl ether to remove unreacted 1-methylimidazole and ethylene glycol monomethyl ether methanesulfonate. The remaining ionic liquid was dried at 60 C. in vacuum (yield: 96%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In dichloromethane; at 10 - 20℃; for 4h; | Example 1-(1); Synthesis of Ethylene Glycol Monomethyl Ether Methanesulfonate; 1-Methylimidazole (50 g) and methanesulfonyl chloride (66 g) were mixed in dichloromethane in a 500 mL two-bulb flask. After adding ethylene glycol monomethyl ether (42 g) dropwise at 10 C., the mixture was stirred at room temperature for 4 hours. After the reaction was completed, water was added. After stirring for 10 minutes, the solvent layer in which the product was dissolved was separated from the aqueous layer in which the byproduct was dissolved. The product was yielded by removing the solvent at room temperature using an evaporator (yield: 98%), and the byproduct 1-methylimidazolium chloride was recovered as 1-methylimidazole using 40 wt % NaOH aqueous solution and used again (yield: 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | In 1,2-dichloro-benzene; for 1.5h;Reflux; | 4.2 3-(2-Amino-6-oxo-1,6-dihydropyrimidin-4-yl)-1-methyl-1H-imidazolium chloride (10a) A solution of 146 mg (1.0 mmol) of <strong>[1194-21-4]2-amino-6-chloropyrimidin-4(3H)-one</strong> and 410 mg (5.0 mmol) of 1-methyl-1H-imidazole in 15 mL of 1,2-dichlorobenzene was heated at reflux temperature for 1.5 h. After cooling, a fine, nearly white precipitate was deposited, which was filtered off and thoroughly washed with ethyl acetate. Yield: 220 mg (97percent). Dec>302 °C. 1H NMR (400 MHz, DMSO-d6): delta=3.93 (s, 3H, Me), 6.16 (s, 1H, 5-H), 7.42 (s, 2H, NH2), 7.88 (m, 1H, 5'-H), 8.26 (m, 1H, 4'-H), 9.72 (s, 1H, 2'-H), 11.61 (s, 1H, NH) ppm 13C NMR (100 MHz, DMSO-d6): delta=36.4, 89.1, 118.5, 124.7, 135.6, 153.0, 156.4, 163.2 ppm. IR (ATR): 3278, 2909, 1666, 1598, 1538, 1437 cm-1. MS (ESI-MS): m/z=192.1. We described the compound before. 40 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With copper(l) iodide; palladium diacetate; In N,N-dimethyl-formamide; at 20 - 140℃; for 1h;Inert atmosphere; Sealed tube; Microwave irradiation; | General procedure: A 10 mL vial equipped with a small magnetic stirring bar wascharged with the appropriate bromo O-hetarene (1.0 equiv, 100mg), Pd(OAc)2 (5 mol%), and CuI (1.0 equiv). Anhyd DMF (1 mL)and the appropriate 1,3-azole (2.0 equiv) were added, and thevessel was purged with N2 and sealed with a PEEK snap cap. Themixture was stirred for 5 min at r.t. before the vessel was placedin the microwave reactor and the mixture was heated to 140 Cwith stirring for the appropriate time (usually 1 h). The solutionwas then cooled to r.t., diluted with EtOAc (15 mL), washed withsat. aq NH4Cl (2 × 15 mL) and dilute aq Na2S2O3 (10 mL). Theaqueous phases were extracted with EtOAc (2 × 10 mL), and theorganic phases were combined and washed with sat. aq NH4Cl(10 mL) and brine. Some H2O was added if any solids precipitatedduring the extraction. The combined organic phases weredried (MgSO4), filtered, and concentrated. The residue was purifiedby column chromatography (silica gel). |
Tags: 1-Methylimidazole | Imidazole | Osteoclasts/Bone/Osteogenesis | Others | Structure | Steroids | Biological Buffers | Fluorescence Labeling Reagents | Fluorescent Dyes | Small Molecule Positive Drugs | Other Inhibitors/Agonists | 616-47-7
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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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