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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.
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Zhou, Jujun ; Deng, Youchao ; Iyamu, Iredia D. ; Horton, John R. ; Yu, Dan ; Hajian, Taraneh , et al.
Abstract: S-Adenosyl-L-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (6e and 7), we designed an adenosine analog (11a) carrying a 3-phenylpropyl moiety at the adenine N6-amino group, and a 3-(cyclohexylmethyl guanidine)-Et moiety at the sulfur atom off the ribose ring. Compound 11a (IC50 = 0.15 μM) is 10x and 5x more potent against CamA than 6e and 7, resp. The structure of the CamA-DNA-inhibitor complex revealed that 11a adopts a U-shaped conformation, with the two branches folded toward each other, and the aliphatic and aromatic rings at the two ends interacting with one another. 11a occupies the entire hydrophobic surface (apparently unique to CamA) next to the adenosine binding site. Our work presents a hybrid knowledge-based and fragment-based approach to generating CamA inhibitors that would be chem. agents to examine the mechanism(s) of action and therapeutic potentials of CamA in C. difficile infection.
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Purchased from AmBeed: 2086772-26-9 ; 29908-03-0 ; 73-24-5 ; 83948-53-2 ; 39684-80-5 ; 58-61-7 ; 2004-06-0 ; 2038-57-5 ; 199915-38-3 ; 2040291-27-6 ; 3218-02-8 ; 1561178-17-3 ; 58944-73-3
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CAS No. : | 39684-80-5 |
Formula : | C7H14BrNO2 |
M.W : | 224.10 |
SMILES Code : | BrCCNC(OC(C)(C)C)=O |
MDL No. : | MFCD02683428 |
InChI Key : | TZRQZPMQUXEZMC-UHFFFAOYSA-N |
Pubchem ID : | 4103526 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302+H312+H332-H314 |
Precautionary Statements: | P260-P270-P271-P264-P280-P362+P364-P303+P361+P353-P301+P330+P331-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405-P501 |
Class: | 8 |
UN#: | 1759 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
[2-(2-Amino-imidazol-1-yl)-ethyl]-carbamic acid tert-butyl ester (Cpd 5b). To a flask containing 2-anninoinnidazole sulfate 5a (1 g, 3.8 mmol) in DMF (20 ml_) was added sodium hydride (0.65 g, 16.3 mmol) in small portions with stirring. The temperature was maintained below 30 0C during the addition by means of an ice bath. After stirring for 30 minutes at 25-30 0C, the solution was cooled to 0 0C and (2-bromo-ethyl)-carbamic acid tert-butyl ester (1.7 g, 7.6 mmol) in DMF (1 ml_) was added. After stirring for 1 min the cooling bath was removed and the solution was stirred toward rt for 16 h. The reaction was carefully quenched with water (10 ml_), extracted with EtOAc (4 x 10 ml_), dried over sodium sulfate, filtered, and concentrated to a residue. The residue was stored at < 0.5 mm Hg for 24 h to remove residual DMF, then purified by normal phase chromatography to give compound 5b (0.29 g) as a brown glass. HRMS calcd. for Ci0Hi9N4O2 m/z 227.1508 (M+H), found: 227.1518. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To the reaction mixture of <strong>[116632-23-6]3-bromo-5-nitrophenol</strong> (4.Og, 18.35 mmol) in 40 ml of DMF add cesium carbonate (12.0 g, 367. mmol) and stir at room temperature for 30 minutes. To the above reaction mixture was added tert-butyl 2-bromoethylcarbamate (6.16 g, 27.5 mmol), cap with argon balloon and stirred at 40°C for 18 hours or until done by LCMS. Concentrate about half of the DMF off, add 500 ml of ethyl acetate, wash organic layer IM NaOH (3x), water, saturated NaCl, dried with Na2SC^, filtered and concentrated in vaccuo to give crude, tert-butyl 2-(3-bromo-5- nitrophenoxy)ethylcarbamate (6.6 grams) used in the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 16h; | A suspension of (+/-)-tetrahydro~3-furanamine (1.1 g, 8.90 mmol, Small Molecules Inc., NJ, USA), 1 ,1-dimethyIethyl (2-bromoethy.)carbamate (1.995 g, 8.90 mmol), and potassium carbonate (3.69 g, 26.7 mmol) in N.N-dimethylformannide (15 mL) was maintained at 50 °C in a sealed pressure vessel for 16 hours. The mixture was cooled, diluted with ethyi acetate, and poured into water. The organic layer was washed twice with 5percent LiCI (aqueous), dried over sodium sulfate, and taken to a residue under reduced pressure to afford 1 ,1-dimethylethyl [2-(tetrahydro-3- furanylamino)ethyl]carbamate (1.33 g, 5.77 mmol, 65percent yield, roughly 50percent purity) as a clear oil used immediately in the subsequent transformation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step-II: Methyl 2-[2-(tert-butoxycarbonylamino)ethoxy]-4-chloro-benzoate (VII-l-II): To a solution of VII-l -I (126.8 g, 679.6 mmol) in anhydrous DMF (1 L) was added anhydrous K2CO3 (187:5 g, 1.36 mol) and stirred at room temperature for 30 min. Finally, a solution of tert-butyl N-(2-bromoethyl)carbamate (228.4 g, 1.02 mol) in THF (360 mL) was added to it and the reaction mixture was stirred at 65 C for 16 h. The reaction mixture was, then, filtered through celite and the filtrate was concentrated under reduced pressure. Diethyl ether ( 1.5 L) was added to the residue and was washed with water ( 1 L); brine ( 1 L), dried over anhydrous filtered and concentrated under reduced pressure to provide crude intermediate VII- 1 -II (242 g); which was used without further purification. | ||
Step-II: Methyl 2-[2-(tert-butoxycarbonylamino)ethoxy]-4-chloro-benzoate (VII-1-II) To a solution of VII-1-I (126.8 g, 679.6 mmol) in anhydrous DMF (1 L) was added anhydrous K2CO3 (187.5 g, 1.36 mol) and stirred at room temperature for 30 min. Finally, a solution of tert-butyl N-(2-bromoethyl)carbamate (228.4 g, 1.02 mol) in THF (360 mL) was added to it and the reaction mixture was stirred at 65 C. for 16 h. The reaction mixture was, then, filtered through celite and the filtrate was concentrated under reduced pressure. Diethyl ether (1.5 L) was added to the residue and was washed with water (1 L); brine (1 L), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide crude intermediate VII-1-II (242 g); which was used without further purification. | ||
Step-II: Methyl 2-[2-(tert-butoxycarbonylamino)ethoxy]-4-chloro-benzoate (VII-1-II): To a solution of VII-1-I (126.8 g, 679.6 mmol) in anhydrous DMF (1 L) was added anhydrous K2CO3 (187.5 g, 1.36 mol) and stirred at room temperature for 30 min. Finally, a solution of tert-butyl N-(2-bromoethyl)carbamate (228.4 g, 1.02 mol) in THF (360 mL) was added to it and the reaction mixture was stirred at 65 C for 16 h. The reaction mixture was, then, filtered through celite and the filtrate was concentrated under reduced pressure. Diethyl ether (1.5 L) was added to the residue and was washed with water (1 L); brine (1 L), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide crude intermediate VII-1-II (242 g); which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 2. Synthesis of 1-(2-tert-Butoxycarbonylamino-ethyl)-1H-<strong>[50820-65-0]indole-6-carboxylic acid methyl ester</strong> A solution of 1H-Indole-6-carboxylic acid methyl ester (0.503 g, 2.87 mmol) and DMF (9.0 mL) under argon was cooled to 0 C. for 10 min. Sodium hydride (˜48%, 0.190 g, 3.80 mmol) was added and reaction warmed to room temperature for 30 min. 2-(Boc-amino)ethyl bromide (0.787 g, 3.52 mmol) was added and the reaction stirred for 17 hr. The reaction was quenched with H2O and extracted with ethyl acetate (3*). The combined organic layers were washed with H2O and brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (0-50% EtOAc:Hexane). ESI-MS m/z 319 (MH)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; for 4h; | Methyl 4-(2-aminoethoxy)-3-fluorobenzoate (1-51)To a mixture of <strong>[403-01-0]methyl 3-fluoro-4-hydroxybenzoate</strong> (17 mmol), cesium carbonate (25 mmol) and DMF (30 mL) was added tert-butyl (2-bromoethyl)carbamate (20 mmol). The resulting suspension stirred at 60 °C for 4 hrs. The reaction was diluted with water (100 mL) and the resulting precipitate was collected by vacuum filtration. The filter cake was washed with water and dried under vacuum to give pure 1-50. 1-50 (17 mmol) was taken up in dichloromethane (12 mL) and treated with TFA (5 mL). The reaction stirred at room temperature for 30 mins. LCMS showed that the reaction was complete. The reaction was concentrated to dryness. The crude material was taken up in dichloromethane and stirred with solid sodium bicarbonate for 8 hrs to remove any residual TFA. The mixture was filtered and the filtrate was dried to give 1-51 as a clear oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9.41% | Synthesis of compound 74.3. To a suspension of sodium hydride (0.72g, 0.0180mol, 1.2eq) in DMSO (15ml) was added compound 74.2 (3g, 0.0150mol, leq.) at 10C. Suspension was stirred for 20 minutes. Tert-butyl (2-bromoethyl) carbamate (4.14g, 0.018mol, 1.2eq.) was added portion wise. Reaction was stirred for 1 hour at room temperature. After completion of the reaction, reaction mixture was diluted with ethyl acetate (50ml) and washed with water (50 mL x2) followed by brine solution (50ml x2). Organic layer was dried over sodium sulphate and concentrate under reduced pressure at 45C. Crude was purified by column chromatography to afford compound 74.3 (0.420g, 9.41%). MS (ES): m/z = 297.1 [M+H] +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.1% | With potassium carbonate; In acetone; at 65℃; for 3h;Microwave irradiation; | 4-(4-Hydroxy-3-methoxyphenyl)but-3-en-2-one (2, 202.5 mg,0.621 mmol), 2-(boc-amino) and ethyl bromide (274 mg,1.22 mmol) were dissolved in acetone (40 mL), K2CO3(204.5 mg,1.48 mmol) was added and placed in a opened microwave reactor. The mixture under stirring was irradiated at 200 W for 3 h, at a final temperature of 65C. The solid was removed by filtration with a sintered glass Buchner funnel under reduced pressure. The yellow solution was purified by semi-flash chromatography(SiO2; petroleum ether: diethyl ether: several proportions). The fractions that eluted with petroleum ether: diethyl ether 7:3 were gathered and the product purified by preparative chromatography with CHCl3: acetone: trielthylamine (9:1:0.1) affording an yellowsolid of tert-butyl(2-(2-methoxy-4-(3-oxobut-1-en-1-yl)phenoxy)ethyl)carbamate (7, 4 mg, 1.1%). mp 89-92C (CHCl3: acetone). IR (KBr)mmaxcm-1 3447, 2920, 2852, 1636, 1385, 1099, 668. 1H NMR (CDCl3, 300 MHz) d: 7.45(1H, d, J= 16.2 Hz, H-3), 7.10 (1H,dd, J= 8.1 and 1.8 Hz, H-60),7.06 (1H,d, J= 1.8 Hz, H-20), 6.94 (1H, d, J= 8.1 Hz, H-50), 6.59(1H, d, J= 16.2 Hz, H-2), 4.91 (2H,m, H-70), 3.94 (3H, s,30-OCH3), 3.23-3.18 (2H,m, H-70), 2.37 (3H,s, H-100), 2.17 (9H,s, H-100); 13CNMR (75.47 MHz, CDCl3)d: 198.5 (C-1), 160.5 (C-90), 148.2 (C-40), 146.9 (C-30), 143.8 (C-3), 127.0 (C-10), 125.0 (C-2), 123.6 (C-60),114.8 (C-50), 109.3 (C-20), 68.2 (C-70), 56.0 (30-OCH3), 29.7 (C-110), 27.3 (C-100). EI-MS (70e V) m/z (rel. intensity,%): 335 (M+, 26),281 (100), 234 (63), 74 (82). HRMS- ESI (+)m/z: Anal. Calc. for C18H25NO5[MH+Na]+ 358.18109, found 358.16249. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 16h; | To a solution of <strong>[33543-78-1]ethyl 1H-imidazole-2-carboxylate</strong> (500 mg, 3.57 mmol) in DMF (10 mL) were added tert-butyl (2-bromoethyl)carbamate (800 mg, 3.57 mmol) and K2CO3 (986 mg, 7.14 mmol), and the resulting white suspension was stirred at 60 C. for 16 h, allowed to cool to RT, then concentrated under reduced pressure. The residue was purified by SiO2 gel chromatography (20% to 100% EtOAc in hexanes) to give the title compound as a white solid (751 mg, 74%). MS (ES+) C13H21N3O4 requires: 283, found: 284 [M+H]+. |
53% | With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 8h;Inert atmosphere; | tert-Butyl (2-bromoethyl)carbamate (17.59 g, 78.49 mmol) was added to ethyl 1H- imidazole-2-carboxylate (10 g, 71.36 mmol) and K2CO3 (11.83 g, 85.63 mmol) in DMF (200 mL) under nitrogen and the resulting mixture stirred at 80 C for 8 hours. The reaction mixture was diluted with EtOAc (300 mL), and washed sequentially with water (50 mL x 2). The aqueous layer was then further extracted with EtOAc (50 mL x 5). The combined organic phases were dried over MgS04, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in petroleum ether. Pure fractions were evaporated to dryness to afford ethyl 1 -(2-((tert-butoxycarbonyl)amino)ethyl)- lH-imidazole-2-carboxylate (Intermediate 7; 10.7 g, 53%) as a colourless liquid. 1HNMR (400 MHz, DMSO, 21 C) delta 1.20 (3H, t), 1.29 (9H, s), 3.26-3.34 (2H, m) 4.27 (2H, q) ,4.32-4.40 (2H, m), 6.90 (1H, s), 7.06 (1H, s), 7.32 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
NaH (0.27 g, 6.75 mmol) is added portionwise to a solution of 1 H-<strong>[36193-65-4]indole-2-carbonitrile</strong> (0.80 g, 5.63 mmol) in DMF (25 mL) and the RM is stirred at RT for 15 min. A solution of N-Boc-2-bromoethyl-amine (1.30 g, 5.63 mmol) in DMF (10 mL) is added dropwise, and the RM is heated up to 85C and stirred at this temperature for 17 h, then cooled at RT and partitioned between Et^O and H2O. The aqueous layer is re- extracted with Et.20 (x3). The combined organic layers are dried over MgS04, filtered and concentrated under reduced pressure, affording the title compound as a brown oil. LC-MS A: tR = 0.90 min; [M+H-Boc]+ = 186.27. | ||
NaH (0.27 g, 6.75 mmol) is added portionwise to a solution of <strong>[36193-65-4]1H-<strong>[36193-65-4]indole-2-carbonitrile</strong></strong> (0.80 g, 5.63mmol) in DMF (25 mL) and the RM is stirred at RT for 15 mm. A solution of N-Boc-2-bromoethyl-amine (1.30 g, 5.63 mmol) in DMF (10 mL) is added dropwise, and the RM is heated up to 85C and stirred at this temperature for 17 h, then cooled at RT and partitioned between Et20 and H20. The aqueous layer is re-extracted with Et20 (x3). The combined organic layers are dried over MgSO4, filtered and concentrated under reduced pressure, affording the title compound as a brown oil. LC-MS A: tR = 0.90 mm; [M+H-Boc] = 186.27. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; | General procedure: To the mixture of the precursor 10(2.26 g, 10.1 mmol, 1.5 equiv) and tert-butyl 1,2,5-thiadiazolidine-2-carboxylate 1,1-dioxide (1.50 g, 6.75 mmol, 1.0 equiv) in dry DMF(10 mL), was added Cs2CO3 (6.60 g, 20.25 mmol, 3.0 equiv). Themixture was stirred at room temperature overnight, and thenextracted with ethyl acetate. The organic phase was washed withsaturated NaHCO3 and brine, dried over anhydrous Na2SO4, filteredand concentrated. The resulting residue was purified via silica gelchromatography to give 11a as colorless oil (1.96 g, 79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; | General procedure: To the mixture of the precursor 10(2.26 g, 10.1 mmol, 1.5 equiv) and tert-butyl 1,2,5-thiadiazolidine-2-carboxylate 1,1-dioxide (1.50 g, 6.75 mmol, 1.0 equiv) in dry DMF(10 mL), was added Cs2CO3 (6.60 g, 20.25 mmol, 3.0 equiv). Themixture was stirred at room temperature overnight, and thenextracted with ethyl acetate. The organic phase was washed withsaturated NaHCO3 and brine, dried over anhydrous Na2SO4, filteredand concentrated. The resulting residue was purified via silica gelchromatography to give 11a as colorless oil (1.96 g, 79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 2h; | To a solution of <strong>[2346-26-1]oxazolidine-2,4-dione</strong> (cas: 2346-26-1, 0.1 g, 0.99 O^N^^BOC mmol) in DMF (5 mL) was added /er/-butyl (2-bromoethyl) carbamate ^ (cas: 39684-80-5, 0.265 g, 1.2 equiv.) and K2CO3 (0.274 g, 2.0 equiv.). The reaction mixture was heated to 70 C for 2 hours. The reaction mixture was then cooled to ambient temperature, and quenched with water (20 mL). The aqueous phase was extracted with EtOAc (3 x 20 mL). The combined organic extracts were washed with water, brine, dried (Na2S04), and concentrated under reduced pressure to afford a residue, which was purified by preparative TLC (Petroleum: EtOAc =1 : 1) to provide carbamate 1-280 as a pale yellow oil (0.1 g, 41 % yield). MS (ESI, pos. ion) m/z: 267(M+Na). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 8h; | A solution of l-<strong>[59702-07-7]methylpiperazin-2-one</strong> (cas: 5625-67-2, 1 g, 9.99 mmol), tert- butyl (2-bromoethyl)carbamate (cas: 39684-80-5, 2 g, 0.9 equiv.) in anhydrous DMF (15 mL) was added K2CO3 (8.28 g, 6.0 equiv.). The reaction mixture was stirred for 8 hours at ambient temperature. Once LC-MS analysis indicated reaction completion, the reaction was quenched with H20 (20 mL) and the aqueous phase was extracted with EtO Ac (20 mL x 3). The combined organic extracts was concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel chromatography (Petroleum ether: EtO Ac = 1 : 10) to provide carbamate 1-333 as a pale oil (0.65 g, 22%). MS (ESI, pos. ion) m/z: 258(M+l). |
Tags: TUN84805 | Aliphatic Chain Hydrocarbons | Carbamates | Esters | Aliphatic Linkers | Organic Building Blocks | Bifunctional Linkers | PROTAC Linkers | 39684-80-5
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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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