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Structure of 4755-77-5
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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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CAS No. : | 4755-77-5 |
Formula : | C4H5ClO3 |
M.W : | 136.53 |
SMILES Code : | O=C(C(Cl)=O)OCC |
MDL No. : | MFCD00000706 |
InChI Key : | OWZFULPEVHKEKS-UHFFFAOYSA-N |
Pubchem ID : | 20884 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H226-H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8(3) |
UN#: | 2920 |
Packing Group: | Ⅱ |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 27.62 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.37 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.49 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.43 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.31 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.09 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.76 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.39 |
Solubility | 5.57 mg/ml ; 0.0408 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.95 |
Solubility | 1.55 mg/ml ; 0.0113 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.9 |
Solubility | 17.4 mg/ml ; 0.127 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.12 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.65 |
* 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 |
---|---|---|
24% | at 70℃; for 5 h; | Step 1 ethyl 5-amino-l,3,4-thiadiazole-2-carboxylate To a solution of hydrazinecarbothioamide (10 g, 54.8 mmol) in POCI3 (25 mL) was added ethyl 2-chloro-2-oxacetate (6.1 mL, 54.8 mmol). The reaction was heated to 70°C and stirred for 5 h. POCI3 was completely removed from the reaction mixture under vacuum. The residue was diluted with ice cold water (150 mL) and basified to pH 8 with saturated sodium bicarbonate solution and then extracted with ethyl acetate (200 mL). The organic layer was separated and dried over a2S04, and the solvent was evaporated to obtain crude product. The crude product was purified by flash chromatography (silica gel 100-200?, 2percent methanol and dichloromethane) to afford ethyl 5-amino-l,3,4-thiadiazole-2-carboxylate as a yellow solid (3.1 g, 24percent yield). ? NMR (400 MHz, DMSO-d6): ? 7.94 (s, 2H), 4.29 (q, 2H), 1.27 (t, 3H); LC- MS m/z calcd for [M+H]+ 174.03, found 174.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With triethylamine In dichloromethane | Example 2 Ii; Compound 4 was prepared according to the Ref: J. Hetero. Chem. 1995, 32, 1693-1702. Then, it was reduced by NaBH4ZLiCl in ethanol solution. Further oxidation by Dess-Martin reagent gave the desired aldehyde 6 in 25 percent overall two-step yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With trichlorophosphate; at 70℃; for 5h; | Step 1 ethyl 5-amino-l,3,4-thiadiazole-2-carboxylate To a solution of hydrazinecarbothioamide (10 g, 54.8 mmol) in POCI3 (25 mL) was added ethyl 2-chloro-2-oxacetate (6.1 mL, 54.8 mmol). The reaction was heated to 70°C and stirred for 5 h. POCI3 was completely removed from the reaction mixture under vacuum. The residue was diluted with ice cold water (150 mL) and basified to pH 8 with saturated sodium bicarbonate solution and then extracted with ethyl acetate (200 mL). The organic layer was separated and dried over a2S04, and the solvent was evaporated to obtain crude product. The crude product was purified by flash chromatography (silica gel 100-200?, 2percent methanol and dichloromethane) to afford ethyl 5-amino-l,3,4-thiadiazole-2-carboxylate as a yellow solid (3.1 g, 24percent yield). ? NMR (400 MHz, DMSO-d6): ? 7.94 (s, 2H), 4.29 (q, 2H), 1.27 (t, 3H); LC- MS m/z calcd for [M+H]+ 174.03, found 174.1. |
at 160℃; for 5h; | EXAMPLE 67-( { [5-( 1 -Ethyl- 1 -hvdroxypropyl)- 1.3.4-thiadiazol-2-yl]amino 1 methyl)-4-phenylquinoline-2-carbonitrile Step 1: Ethyl 5-amino-1.3.4-thiadiazole-2-carboxylateN-NQ S NH,EtOA mixture of ethyl chloro(oxo)acetate (0.5 g, 3.68 mmol) and hydrazinecarbothioamide (0.335 g, 3.68 mmol) was heated to 160° C for 5 h. The solvent was removed under reduce pressure and the crude purified on silica gel (eluting with 3percent methanol in DCM) to give the title product. 1H NMR (400 MHz, acetone-ds): delta 7.28 (bs, IH), 9.67 (bs, IH), 4.39 (q, 2H), 1.38 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 47 2'-Carbamoyl-4'-nitrooxanilic acid ethyl ester. 59 <strong>[16313-65-8]<strong>[16313-65-8]2-Amino-5-nitrobenzamid</strong>e</strong> (5.43 g. 0.03 mole) is condensed with 3.7 ml (0.033 mole) of ethyl oxalyl chloride in a manner similar to example 3, giving 6.54 g of the title compound, m.p. 206-209 C., after crystallization from ethanol. Elemental Analysis for C11 H11 N3 O6: Calc'd: C, 46.98; H, 3.94; N, 14.94. Found: C, 46.68; H, 3.96; N, 15.12. | ||
EXAMPLE 30 2'-Carbamoyl-4'-nitrooxanilic acid ethyl ester. 59 <strong>[16313-65-8]<strong>[16313-65-8]2-Amino-5-nitrobenzamid</strong>e</strong> (5.43 g., 0.03 mole) is condensed with 3.7 ml. (0.033 mole) of ethyl oxalyl chloride in a manner similar to example 12, giving 6.54 g. of the title compound, m.p. 206-209 C., after crystallization from ethanol. Elemental Analysis for C11 H11 N3 O6: Calc'd: C, 46.98; H, 3.94; N, 14.94: Found: C, 46,68; H, 3.96; N, 15.12. | ||
EXAMPLE 30 2'-Carbamoyl-4'-nitrooxanilic acid ethyl ester. 59 <strong>[16313-65-8]<strong>[16313-65-8]2-Amino-5-nitrobenzamid</strong>e</strong> (5.43 g., 0.03 mole) is condensed with 3.7 ml. (0.033 mole) of ethyl oxalyl chloride in a manner similar to example 12, giving 6.54 g. of the title compound, m.p. 206-209 C., after crystallization from ethanol. Elemental Analysis for C11 H11 N3 O6: Calc'd: C, 46.98; H, 3.94; N, 14.94. Found: C, 46,68; H, 3.96; N, 15.12. |
EXAMPLE 30 2'-Carbamyl-4'-nitrooxanilic acid ethyl ester. 59 <strong>[16313-65-8]<strong>[16313-65-8]2-Amino-5-nitrobenzamid</strong>e</strong> (5.43 g., 0.03 mole) is condensed with 3.7 ml. (0.033 mole) of ethyl oxalyl chloride in a manner similar to example 12, giving 6.54 g. of the title compound, m.p. 206-209 C., after crystallization from ethanol. Elemental Analysis for C11 H11 N3 O6: Calc'd: C, 46.98; H, 3.94; N, 14.94. Found: C, 46,68; H, 3.96; N, 15.12. | ||
EXAMPLE 47 2'-Carbamoyl-4'-nitrooxanilic acid ethyl ester. 59 <strong>[16313-65-8]<strong>[16313-65-8]2-Amino-5-nitrobenzamid</strong>e</strong> (5.43 g, 0.03 mole) is condensed with 3.7 ml (0.033 mole) of ethyl oxalyl chloride in a manner similar to example 3, giving 6.54 g of the title compound, m.p. 206-209 C., after crystallization from ethanol. Elemental Analysis for C11 H11 N3 O6: Calc'd: C, 46.98; H, 3.94; N, 14.94. Found: C, 46.68; H, 3.96; N, 15.12. | ||
With triethylamine; In tetrahydrofuran; at 0℃; for 1h; | Step 2 To a solution of <strong>[16313-65-8]2-amino-5-nitrobenzamide</strong> (18.1 g) and triethylamine (15 mL) in THF (100 mL) was added dropwise a solution of ethyl chloroglyoxylate (14.4 g) in THF (20 mL) under ice-cooling, and the mixture was stirred at 0C for 1hr. 1N Hydrochloric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogencarbonate and saturated brine, dried, and concentrated. The obtained crude crystals were washed with diisopropyl ether to give ethyl [2-(aminocarbonyl)-4-nitrophenyl]amino}(oxo)acetate (8.1 g). 1H-NMR (300MHz, DMSO-d6) delta: 1.37 (3H, t, J = 7.1 Hz), 3.33 (3H, s), 4.41 (2H, q, J = 7.1 Hz), 8.03 (1H, d, J = 8.8 Hz), 8.59 (1H, dd, J = 8.8, 2.7 Hz), 8.83 (1H, d, J = 2.2 Hz). | |
8.1 g | With triethylamine; In tetrahydrofuran; at 0℃; for 1h; | Step 2 To a solution of <strong>[16313-65-8]2-amino-5-nitrobenzamide</strong> (18.10 g) and triethylamine (15 ml) in THF (100 mL) was added dropwise a solution of ethyl chloroglyoxylate (14.36 g) in THF (20 ml) under ice-cooling, and the mixture was stirred at 0 C. for 1 hr. 1N Hydrochloric acid was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogen carbonate and saturated brine, dried and concentrated. The obtained crude crystals were washed with diisopropy ether to give ethyl [2-(aminocarbonyl)-4-nitrophenyl]amino}(oxo)acetate (8.1 g). 1H NMR (300 MHz, DMSO-d6) delta: 1.4 (t, J=7.1 Hz, 2H) 3.3 (s, 3H) 4.4 (q, J=7.1 Hz, 2H) 8.0 (d, J=8.8 Hz, 1H) 8.6 (dd, J=8.8, 2.7 Hz, 1H) 8.8 (d, J=2.2 Hz, 1H) |
EXAMPLE 47 2'-Carbamoyl-4'-nitrooxanilic acid ethyl ester. 59 <strong>[16313-65-8]<strong>[16313-65-8]2-Amino-5-nitrobenzamid</strong>e</strong> (5.43 g, 0.03 mole) is condensed with 3.7 ml (0.033 mole) of ethyl oxalyl chloride in a manner similar to example 3, giving 6.54 g of the title compound, m.p. 206-209C., after crystallization from ethanol. Elemental Analysis for C11 H11 N3 O6: Calc'd: C, 46.98; H, 3.94; N, 14.94. Found: 46.68; H, 3.96; N, 15.12. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 36 2'-Cyano-3'-methoxyoxanilic acid ethyl ester. 80/71 2-Amino-6-methoxybenzonitrile (4.67 g, 0.0315 mole) is condensed with 3.88 ml (0.0346 mole) of ethyl oxalylchloride in a manner similar to example 3, giving 5.0 g of the title compound, m.p. 142-145 C., after crystallization from toluene. Elemental Analysis for C12 H12 N2 O4: Calc'd: C, 58.06; H, 4.87; N, 11.29. Found: C, 58.21; H, 4.93; N, 11.02. | ||
EXAMPLE 36 2'-Cyano-3'-methoxyoxanilic acid ethyl ester. 80/71 2-Amino-6-methoxybenzonitrile (4.67 g, 0.0315 mole) is condensed with 3.88 ml (0.0346 mole) of ethyl oxalylchloride in a manner similar to example 3, giving 5.0 g of the title compound, m.p. 142-145C., after crystallization from toluene. Elemental Analysis for C12 H12 N2 O4: Calc'd: C, 58.06; H, 4.87; N, 11.29. Found: C, 58.21; H, 4.93; N, 11.02. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With pyridine; at 0 - 20℃; for 15h; | Step 1. To a suspension of commercially available 3-aminopyridine-4-carboxylic acid (4.84 g, 35.1 mmol) in pyridine (60 mL) wasadded dropwise ethyl chloroglyoxylate (9.58 g, 70.2 mmol) at 0 C,and the mixture was stirred at room temperature for 15 h. Thereaction mixture was concentrated under reduced pressure andthe residue was suspended with water. The resulting precipitatewas collected by filtration to give 3-(2-ethoxy-2-oxoacetamido)pyridine-4-carboxylic acid as a pale yellow powder (3.74 g,45percent). 1H NMR (200 MHz, DMSO-d6) d 1.33 (3H, t, J = 7.0 Hz), 4.33(2H, q, J = 7.0 Hz), 7.88 (1H, d, J = 5.0 Hz), 8.53 (1H, d, J = 5.0 Hz),9.71 (1H, s), 12.10 (1H, s). |
45% | With pyridine; at 35℃; for 15h;Cooling with ice; | Step 2 To a suspension (60 mL) of 3-aminoisonicotinic acid (4.84 g, 35.1 mmol, 100percent) in pyridine was added dropwise ethyl chloroglyoxylate (9.58 g, 70.2 mmol) under ice-cooling, and the mixture was stirred at room temperature for 15 hrs. The reaction mixture was concentrated under reduced pressure and water was added to the concentrated residue to give a suspension. The insoluble material was collected by filtration to give, 3-[(ethyloxy)(oxo)acetyl]amino}pyridine-4-carboxylic acid as a pale-yellow powder (3.74 g, 45percent). 1H-NMR (200 MHz, DMSO-d6) delta: 1.33 (3H, t, J=7.0 Hz), 4.33 (2H, q, J=7.0 Hz), 7.88 (1H, d, J=5.0 Hz), 8.53 (1H, d, J=5.0 Hz), 9.71 (1H, s), 12.10 (1H, s). |
With triethylamine; In tetrahydrofuran; water; | Example 33 3-(Oxalyl-amino)-isonicotinic acid; To a stirred solution of 3-amino-isonicotinic acid (0.5 g, 3.62 mmol) and triethylamine (1 ml) in dry tetrahydrofuran (50 ml) at 0° C. was added dropwise ethyl oxalyl chloride (0.5 g, 3.69 mmol). The resulting reaction mixture was stirred at room temperature for 3 h, filtered and the volatiles were evaporated in vacuo. To the residue was added water (50 ml) and the resulting mixture was extracted with diethyl ether (2*50 ml). The organic phase was washed with saturated aqueous sodium chloride (50 ml), dried (MgSO4), filtered and the solvent evaporated in vacuo affording 0.4 g (46percent) of 3-(ethoxyoxalyl-amino)-isonicotinic acid as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine; In dichloromethane;Cooling; | 1 -Methyl-3-phenylpiperazine (123.2 g; 0.70 mol) was dissolved in 500 dichloromethane. Triethylamine (30 ml; ca 0.2 mol) was added. A solution of ethyl chlorooxalate (107 g; 0.78 mol) in dichloromethane was slowly added under cooling. At 2/3 of the total addition a thick suspension was formed. Even after addition of more solvent, stirring remained difficult. The mixture was quenched with 10percent sodium carbonate. The organic layer is washed again with carbonate, dried and evaporated to an orange oil (191.2 g; 0.69 mol; 99 percent). Crystallisation with seeding proved difficult. Deep evaporation and storage as oil.TLC: very pure, a small amount of coloured polar material on baseline. No trace of the dioxamide (prepared from oxalylchloride and piperazine). GC: 18.0/18.2 min, 0.36 areapercent of 3.8 min impurity. A small sample (20 g) was stirred with water to induce crystallisation. <n="15"/>mp ca 45 °C. The main bulk of the oil solidified after a few days of standing. Melting was needed before use. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; In tetrahydrofuran; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol; | EXAMPLE 2A Ethyl 3-(acetylamino)-2-oxopentanoate 9,2 g (63,4 mmol) 2-(Acetylamino)butanoic acid are suspended in 120 ml tetra-hydrofurane and heated to reflux together with 15,0 g (190 mmol) pyridine and a bit of N,N-dimethylaminopyridine. While heating at reflux, 17,3 g (127 mmol) ethyl chloro(oxo)acetate are added dropwise. The reaction mixture is heated at reflux until no more evolution of gas can be observed. After cooling down to room temperature, the reaction mixture is added to ice water and the organic phase extracted with ethyl acetate. The dried organic phase is evaporated to dryness in vacuo, dissolved in ethanol and the solution directly used for the next reaction. | |
With pyridine; dmap; In tetrahydrofuran;Heating / reflux; | Example 2A; Ethyl 3- (acetylamino)-2-oxop entano ate; 9.2 g (63.4 mmol) 2- (Acetylamino) butanoic acid are suspended in 120 ml tetra- hydrofuran and heated to reflux together with 15.0 g (190 mmol) pyridine and a bit of N, N-dimethylaminopyridine. While heating at reflux, 17. 3 g (127 mmol) ethyl chloro (oxo) acetate are added dropwise. The reaction mixture is heated at reflux until no more evolution of gas can be observed.. After cooling down to room temperature, the reaction mixture is added to ice water and the organic phase extracted with ethyl acetate. The dried organic phase is evaporated to dryness in vacuo, dissolved in ethanol and the solution directly used for the next reaction. | |
With pyridine; dmap; In tetrahydrofuran;Heating / reflux; | Example 2A; Ethyl 3-(acetylamino)-2-oxopentanoate; 9.2 g (63.4 mmol) 2-(Acetylamino) butanoic acid are suspended in 120 ml tetrahydro- furan and heated to reflux together with 15. 0 g (190 mmol) pyridine and a bit of N, N- dimethylaminopyridine. While heating at reflux, 17.3 g (127 mmol) ethyl chloro- (oxo) acetate are added dropwise. The reaction mixture is heated at reflux until no more evolution of gas can be observed. After cooling down to room temperature, the reaction mixture is added to ice water and the organic phase extracted with ethyl acetate. The dried organic phase is evaporated to dryness in vacuo, dissolved in ethanol and the solution directly used for the next reaction. |
With pyridine;dmap; In tetrahydrofuran;Heating / reflux; | 9.2 g (63.4 mmol) 2- (acetylamino) butanoic acid are suspended in 120 ml tetrahydro- furan and heated to reflux together with 15.0 g (190 mmol) pyridine and a bit of N, N- dimethylaminopyridine. While heating at reflux, 17.3 g (127 mmol) ethyl chloro- (oxo) acetate are added dropwise. The reaction mixture is heated at reflux until no more evolution of gas can be observed.. After cooling down to room temperature, the reaction mixture is added to ice water and the organic phase extracted with ethyl acetate. The dried organic phase is evaporated to dryness in vacuo, dissolved in ethanol and the solution directly used for the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With magnesium; In water; cadmium(II) chloride; benzene; | Method A Grignard reagent was prepared in conventional manner as follows: The dichloroiodobenzene was added to magnesium over 1-2 hours and the resulting solution was refluxed for about 4 hours. As all the Mg had not dissolved the Grignard was allowed to stir at room temperature overnight. The flask was then cooled in ice and the dry cadmium chloride added portionwise over 10 minutes. When all the cadmium chloride had been added the reaction mixture was allowed to warm to room temperature and was then heated under reflux for 45 minutes. The ether was evaporated off and the residue washed twice with dry benzene which, in was turn, also evaporated off. The residue was then taken and treated with ethyl oxalyl chloride in 20 mls dry benzene. This was added slowly from a dropping funnel with stirring. The reaction was very vigorous. When addition was complete and spontaneous reflux had subsided the reaction mixture was refluxed for a further hour. The reaction mixture was then cooled in an ice bath. Ice/water was carefully added. Sufficient 20percent H2 SO4 was then added to give two clear phases. The aqueous phase was separated and extracted twice with benzene. The benzene layers were combined and extracted 1*water, 1*Na2 CO3 solution, 1*water and 1*NaCl solution. The benzene solution was then dried over MgSO4, filtered and evaporated down. 17.5 g crude material was obtained. NMR and TLC analyses were performed. TLC in Si/CHCl3 gave two spots, one corresponding to the title compound (product) and one to the dichloroiodobenzene (starting material). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-ethyl-N,N-diisopropylamine; at 20℃; for 0.25h; | Ethyl oxalyl chloride (44 mL, 390 mmol) was added to a solution of <strong>[168268-00-6]4-benzyloxy-3-fluoroaniline</strong> (44 g, 180 mmol) in diisopropylethylamine (69 mL, 400 mmol) and stirred at room temperature for 15 min. The mixture was extracted with dichloromethane and washed with water and brine. The organic layer was dried over sodium sulfate and concentrated to afford ethyl [(4- benzyloxy-3-fluorophenyl)amino](oxo)acetate (58.4 g, 100 %). 1H NMR (400 MHz, J6- DMSO): delta 10.87 (s, IH), 7.73 (d, IH), 7.69 (d, IH), 7.53 (d, IH), 7.46-7.40 (m, 4H), 5.17 (s, 2H), 4.31 (q, 2H), 1.31(t, 3H); IR (cm"1): 1732, 1705, 1558, 154I, 1508, 1456, 1273, 1186, 1167, HOl, 999, 858, 741, 694; LC/MS (M+H = 318). |
100% | With N-ethyl-N,N-diisopropylamine; at 20℃; for 0.25h; | Ethyl oxalyl chloride (44 mL, 390 mmol) was added to a solution of <strong>[168268-00-6]4-benzyloxy-3-fluoroaniline</strong> (44 g, 180 mmol) in DIISOPROPYLETHYLAMINE (69 mL, 400 mmol) and stirred at room temperature for 15 min. The mixture was extracted with dichloromethane and washed with water and brine. The organic layer was dried over sodium sulfate and concentrated to afford ethyl [ (4- benzyloxy-3-fluorophenyl) amino] (oxo) acetate (58. 4 g, 100 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With HF; SF4; nitric acid; acetic anhydride; In ethanol; acetic acid; | Those of the starting materials which are of the formula SPC10 are prepared by the following reaction scheme; SPC11 In a representative preparation, ethyl N-(4-difluoromethyl-2-nitrophenyl)oxamide was prepared as described below. p-Nitrobenzal fluoride (5 grams) (prepared by reaction of p-nitrobenzaldehyde with SF4 /HF) was hydrogenated over 200 mg. platinum oxide in 50 ml. of ethanol. The catalyst was removed by filtration and the ethanol, by evaporation. The residue was dissolved in 50 ml. of cold ether; to this solution was added a solution of ethyl oxalyl chloride (7 ml.) in 25 ml. of ether. The reaction mixture was stirred for 15 minutes, filtered, and evaporated to dryness. The residue, the desired ethyl N-(p-difluoromethylphenyl)oxamide product, was recrystallized from a mixture of ethanol and water, m.p. 110-114C. Ethyl N-(p-difluoromethylphenyl)oxamide (1 gram) was dissolved in 4 ml. of each of acetic acid and acetic anhydride and the mixture cooled to about 0-5C. Fuming nitric acid (1 ml.) mixed with acetic acid (2 ml.) was added portionwise to the cooled solution. An additional 1 ml. of fuming nitric acid was added one hour later. Two hours after the initial addition, the reaction mixture was poured into water, and the ethyl N-(4-difluoromethyl-2-nitrophenyl)oxamide product was collected, washed, and recrystallized from a mixture of ethanol and water, m.p. 113-115C. Those starting materials which are 1-methylquinoxalinones: SPC12 are prepared in accordance with the following procedures SPC13 The following preparation of 1-methyl-7-trifluoromethyl-2(1H)-quinoxalinone illlustrates the procedure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 20℃; | [00374] Step B: To a solution of <strong>[1885-32-1]2-amino-3-methylbenzamide</strong> (1.50 g, 10.0 mmol) and DIEA (2.61 mL, 15 mmol) in THF (50 mL) at 0 0C was added ethyl chlorooxoacetate (1.23 mL, 11.0 mmol). The solution was allowed to warm to rt and stir for 16 h, then was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 20 -100% EtOAc/hexanes to afford ethyl 2- (2-carbamoyl-6-methylphenylamino)-2-oxoacetate as a solid (490 mg, 20%). 1H NMR (300 MHz, DMSO-J6) delta 1.31 (t, J = 7.1 Hz, 3H), 2.17 (s, 3H), 4.30 (q, J = 7.1 Hz, 2H), 7.28 (t, IH), 7.33 - 7.57 (m, 3H), 7.82 (s, IH), 10.67 (s, IH). |
20% | With DIEA; In tetrahydrofuran; | Step B: To a solution of <strong>[1885-32-1]2-amino-3-methylbenzamide</strong> (1.50 g, 10.0 mmol) and DIEA (2.61 mL, 15 mmol) in THF (50 mL) at 0 C. was added ethyl chlorooxoacetate (1.23 mL, 11.0 mmol). The solution was allowed to warm to room temperature and stir for 16 hrs, then was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 20-100% EtOAc/hexanes to afford ethyl 2-(2-carbamoyl-6-methylphenylamino)-2-oxoacetate as a solid (490 mg, 20%). 1H NMR (300 MHz, DMSO-d6) delta1.31 (t, J=7.1 Hz, 3H), 2.17 (s, 3H), 4.30 (q, J=7.1 Hz, 2H), 7.28 (t, 1H), 7.33-7.57 (m, 3H), 7.82 (s, 1H), 10.67 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 20℃; | [00394] Step B: To a solution of <strong>[5900-59-4]2-amino-4-chlorobenzamide</strong> (393 mg, 2.30 mmol) and DIEA (0.60 mL, 3.45 mmol) in THF (15 mL) at 0 0C was added ethyl chlorooxoacetate (0.28 mL, 2.53 mmol). The solution was allowed to warm to rt and stir for 2 h. The mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 10-50percent EtOAc/hexanes to afford ethyl 2-(2-carbamoyl-5-chlorophenylamino)-2-oxoacetate as a solid (545 mg, 88percent). 1H NMR (300 MHz, DMSO-d6) delta 1.32 (t, J= 6.97 Hz, 3 H), 4.31 (q, J= 6.97 Hz, 2 H), 7.34 (d, J= 8.48 Hz, 1 H), 7.86 - 8.03 (m, 2 H), 8.44 (br s, 1 H), 8.62 (s, 1 H), 13.24 (s, 1 H) |
88% | With DIEA; In tetrahydrofuran; | Step B:To a solution of <strong>[5900-59-4]2-amino-4-chlorobenzamide</strong> (393 mg, 2.30 mmol) and DIEA (0.60 mL, 3.45 mmol) in THF (15 mL) at 0° C. was added ethyl chlorooxoacetate (0.28 mL, 2.53 mmol).The solution was allowed to warm to room temperature and stir for 2 hrs.The mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 10-50percent EtOAc/hexanes to afford ethyl 2-(2-carbamoyl-5-chlorophenylamino)-2-oxoacetate as a solid (545 mg, 88percent).1H NMR (300 MHz, DMSO-d6) 81.32 (t, J=6.97 Hz, 3H), 4.31 (q, J=6.97 Hz, 2H), 7.34 (d, J=8.48 Hz, 1H), 7.86-8.03 (m, 2H), 8.44 (br s, 1H), 8.62 (s, 1H), 13.24 (s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With sodium acetate; acetic acid; at 35 - 90℃; for 1.75h; | General procedure: 6-Amino-3H-1,3-benzoxazol-2-one (700 mg, 4.66 mmol) and sodium acetate (497 mg, 6.05 mmol) were dissolved in acetic acid (20 mL) at 35 °C. Ethyl chlorooxoacetate (677 muL, 6.05 mmol) was added dropwise and the reaction mixture was stirred at 35 °C for 1 h and 45 min at 90 °C then water (50 mL) was added to the solution. The precipitate was filtered, washed with water (2 .x. 30 mL) and dried overnight under vacuum in presence of P2O5 to afford the intermediate ethyl 2-acetamido-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetate (857 mg, 74percent) as a white solid. A solution of potassium hydroxide (101 mg, 1.80 mmol) in water (400 muL) was added to a suspension of ethyl 2-acetamido-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetate obtained above (150 mg, 0.60 mmol) in ethanol (3 mL) and the reaction mixture was stirred at room temperature for 2 h. Water (5 mL) was added to the mixture and the resulting homogenous solution was acidified to pH = 1 with concentrated HCl. The precipitate was filtered and dried overnight under vacuum in presence of P2O5 to give 4a (115 mg, 87percent) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium acetate; acetic acid; at 35 - 90℃; for 1.75h; | General procedure: 6-Amino-3H-1,3-benzoxazol-2-one (700 mg, 4.66 mmol) and sodium acetate (497 mg, 6.05 mmol) were dissolved in acetic acid (20 mL) at 35 C. Ethyl chlorooxoacetate (677 muL, 6.05 mmol) was added dropwise and the reaction mixture was stirred at 35 C for 1 h and 45 min at 90 C then water (50 mL) was added to the solution. The precipitate was filtered, washed with water (2 × 30 mL) and dried overnight under vacuum in presence of P2O5 to afford the intermediate ethyl 2-acetamido-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetate (857 mg, 74%) as a white solid. A solution of potassium hydroxide (101 mg, 1.80 mmol) in water (400 muL) was added to a suspension of ethyl 2-acetamido-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetate obtained above (150 mg, 0.60 mmol) in ethanol (3 mL) and the reaction mixture was stirred at room temperature for 2 h. Water (5 mL) was added to the mixture and the resulting homogenous solution was acidified to pH = 1 with concentrated HCl. The precipitate was filtered and dried overnight under vacuum in presence of P2O5 to give 4a (115 mg, 87%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 6h; | General procedure: To a stirred solution of 3,4-dichloroaniline 4b (1.94 g, 12.0 mmol) in THF (20.0 mL) were added ethyl chloroglyoxylate (1.11 mL, 10.0 mmol) and Et3N (15.2 mL, 11.0 mmol) at 0 °C. The mixture was stirred at room temperature for 6 h. After the precipitate was filtrated off, the filtrate solution was concentrated under reduced pressure. The residue was dissolved in EtOAc, and washed with 1.0 M HCl, saturated NaHCO3 and brine, then dried over MgSO4. Concentration under reduced pressure to provide the title compound 6b (1.58 g, 95percent yield) as white powder, which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With sodium hydrogencarbonate; In tetrahydrofuran; water; at 0 - 20℃; | Step 1 3-(3-Bromophenyl)-2-(2-ethoxy-2-oxoacetamido)propanoic acid [0396] To a suspension of <strong>[30163-20-3]2-amino-3-(3-bromophenyl)propanoic acid</strong> (11.0 g, 45.5 mmol) and NaHCO3 (11.5 g, 136.5 mmol) in THF (100 mL)/ H2O (100 mL), ethyl 2-chloro-2-oxoacetate (18.4 g, 135.2 mmol) was added dropwise at 0 C. The mixture was stirred at RT overnight, acidified with aqueous critic acid (10%), and then extracted with EtOAc (3×100 mL). The combined organic layers were washed with H2O (100 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated to afford the crude product, which was purified by Combiflash reverse phase chromatography (50%60% MeCN/H2O containing 0.01% TFA) to afford 3-(3-bromophenyl)-2-(2-ethoxy-2-oxoacetamido)propanoic acid as a colorless oil (5.2 g, 33%). MS (ES+) C13H14BrNO5 requires: 343, 345. found: 344 [M+H]+, 346 [M+2+H]+(1:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | EXAMPLE 1 Preparation of ethyl {5-hydroxy-6-oxo-l-[4-(2-oxopiperidin-l-yl)phenyl] -1,2,3,6- tetrahydropyridin-4-yl}(oxo)acetate. 5,6-Dihydro-3-(4-mophiholinyl)-l-[4-(2-oxo-l-piperidinyl)phenyl]-2(lH)-pyridinone (100 gm) is stirred with Ethyl oxalyl chloride (42.24 gm) in dichloromethane (800 ml) in the presence of Pyridine (26.7 gm) at 25-30C for 3 hrs. After the reaction completion dichloromethane is distilled completely and Ethyl acetate (100 ml) is added. To this 10 % HCI solution (500 ml) is added and stirred for 1 nr. The solid is filtered and dried. Yield 90% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
890 mg | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; | (2S,3S)-methyl 2-methyl-l-((S)-l-phenylethyl)pyrrolidine-3-carboxylate (1.9 g, 7.68 mmol) was dissolved in methanol (50 mL). This was added to Pd/C (10% / 0.82 g, 0.77 mmol) under nitrogen. The mixture was stirred under a hydrogen atmosphere at room temperature for 24 hours._The resulting mixture was filtered over a dicalite plug and rinsed using of methanol (100 mL). The filtrate was concentrated in vacuo yielding <strong>[143878-87-9]methyl (2S,3S)-2-methylpyrrolidine-3-carboxylate</strong> (830 mg) as a clear oil. Ethyl 2-chloro-2-oxo- acetate (1.3 mL, 11.59 mmol) was added drop wise to a solution of methyl (2S,3S)-2- methylpyrrolidine-3-carboxylate (0.83 g, 5.8 mmol) and diisopropylethylamine (4.99 mL, 28.98 mmol) in dry dichloromethane (5 mL) at room temperature. The reaction mixture was stirred at room temperature for 1 h. Saturated aqueous NaHC03 (5 mL) were added to the reaction mixture and the layers were separated. Then it was extracted using dichloromethane (2 X 10 mL). The combined extracts were dried on Na2S04, filtered and concentrated in vacuo. The obtained crude was purified by silica gel column chromatography using gradient elution from heptane to EtOAc. (100:0 to 0: 100). The desired fractions were concentrated in vacuo yielding methyl (2S,3S)-l-(2-ethoxy-2-oxo-acetyl)-2-methyl-pyrrolidine-3-carboxylate (890 mg) of as a yellow oil. methyl (2S,3S)-l-(2-ethoxy-2-oxo-acetyl)-2-methyl-pyrrolidine-3-carboxylate (250 mg, 1 mmol) was dissolved in ethanol (10 mL) and isopropylamine (1698 mu, 19.94 mmol) and the mixture was stirred at 60C for 2 hours. The mixture was concentrated in vacuo. The obtained oil was purified by silica gel column chromatography using gradient elution from heptane to EtOAc. (100:0 to 0: 100). The desired fractions were concentrated under reduced pressure yielding methyl (2S)-l-[2-(isopropylamino)-2-oxo-acetyl]-2-methyl- pyrrolidine-3-carboxylate (380 mg) as a clear oil which was used as such. Methyl (2S)-l-[2-(isopropylamino)-2-oxo-acetyl]-2-methyl-pyrrolidine-3-carboxylate (0.38 g, 1.48 mmol) was dissolved in tetrahydrofuran (10 mL) and this was stirred at room temperature. To this was added LiOH (178mg, 7.41 mmol) in water (2 mL) followed by methanol (2 mL). The resulting mixture was stirred at room temperature for 2 hours. Then, HC1 (1M in H20) (7.41 mL, 1 M, 7.41 mmol) was added and the mixture was concentrated in vacuo until only water remained. Water (5 mL) was added and this solution was extracted using 2-methyl-tetrahydrofuran (3 x 15 mL). The combined extracts were washed with brine (15 mL), dried on Na2S04, filtered and concentrated in vacuo yielding (2S)- 1 -[2-(isopropylamino)-2-oxo-acetyl]-2-methyl-pyrrolidine-3-carboxylic acid (312 mg) which was used as such. (2S)- 1 -[2-(isopropylamino)-2-oxo-acetyl]-2-methyl-pyrrolidine-3-carboxylic acid (104 mg, 0.43 mmol) was dissolved in Nu,Nu-dimethylformamide (1 mL). Then HATU (0.18 g, 0.47 mmol) was added and this mixture was stirred for 20 minutes. Then DIPEA (0.22 mL, 0.75 g/mL, 1.29 mmol) was added folowed by 5-amino-2-fluorobenzonitrile (0.12 g, 0.86 mmol). The reaction mixture was stirred at 50C for 4 hours. Then this mixture was cooled to room temperature and injected directly onto a silica plug. The mixture was purified by silica gel column chromatography using gradient elution from heptane to EtOAc. (100:0 to 0: 100) and further by preperative HPLC (Stationary phase: RP SunFire Prep C18 OBD-IotaOmicronmuiotaeta, 30x150mm, Mobile phase: 0.25% NH4HC03 solution in water, MeOH) The desired fractions were concentrated under reduced pressure and co- evaporated twice with methanol (2 X 15mL) and dried in a vacuum oven at 55C for 18 hours yielding compound 27 (57 mg) as a white powder. Method B, Rt = 0.81 (31 %) and 0.83 min (69 %), m/z = 359.2 (M-H)~, Exact mass: 360.2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 1.0h; | 5-Bromo-4-chloro-3-aminopyridine (4.1 g, 0.020 mol)Was dissolved in 100 mL of tetrahydrofuran,Triethylamine (2.4 g, 0.024 mol) was added,The system was placed in an ice bath at 0 ° C,A solution of oxalyl chloride monoethyl ester (3.0 g, 0.022 mol)In tetrahydrofuran solution,Reaction at room temperature for 1 hour,Concentrated under reduced pressure,Ethyl acetate (100 mL) was added,Washed with saturated sodium bicarbonate solution (50 mL * 2 times)Dispensing,The organic phase was dried over anhydrous sodium sulfate,Concentrated under reduced pressure to dry,To give 5.5 g of crude solid,Yield 90.0percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: A mixture of2-(tert-butyl)aniline(15.00 g, 100.52 mmol, 15.63 mL, 1.00eq), Et3N (11.19 g, 110.57 mmol, 15.33 mL, 1.10eq) and DCM (150.00 mL) was stirred at 0 ? 5 °C for 15 minutes; ethyl 2-chloro-2-oxo-acetate (13.72 g, 100.52 mmol, 11.25 mL, 1.00eq) was added to the reaction mixture dropwise during 15 minutes. This mixture was stirred at 20 °C for 16 h. The mixture was quenched with water (100 mL). The mixture was extracted with EtOAc (200 mL * 2). The organic layers was combined, washed with 0.1 M HCl (150 mL) and water (100 mL). The organic phase was dried over Na2SO4, filtered and concentrated by vacuum to give ethyl 2-(2-tert-butylanilino)-2-oxo-acetate (25.00 g, crude) as a colorless oil. A mixture of ethyl 2-(2-tert-butylanilino)-2-oxo-acetate (25.00 g, 100.28 mmol, 1.00eq) and 1,4-dioxane (250.00 mL) was stirred at 20 °C for 5 minutes. A solution of LiOH·H2O (4.21 g, 100.28 mmol, 2.79 mL, 1.00eq) in Water (125.00 mL) was added to the mixtue. The reaction mixture was stirred at rt for 1.5 h. 400 mL water was added the reaction mixture ,the mixture was washed with 300 mL EtOAc. The aqueous layer was adjusted pH to 2 by HCl (12 M), then, extracted with EtOAc (300 mL * 2). The organic layers was combined, washed with 200 mL water. The organic layer was dried, filtered and the filtrate was concentrated by vacuum to give2-((2-(tert-butyl)phenyl)amino)-2-oxoacetic acid (14)(21.00 g, 94.92 mmol, 95percent yield) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With triethylamine; In dichloromethane; at 0 - 15℃; for 16h; | Compound 88-a (1.00 g, 5.11 mmol, 1.00 eq) was dissolved in dichloromethane (25.00 mL), and triethylamine (1.03 g, 10.22 mmol, 1.42 mL, 2.00 eq) and compound 1-b (837.74 mg, 6.13 mmol, 686.67 mL, 1.20 eq) were successively added to the above solution at 0°C. The reaction solution was maintained at 15°C and stirred for 16 hours. After the reaction was completed, the reaction solution was added with water (100 mL), and extracted with dichloromethane (100 mL 3 3). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product. The crude product was subjected to column chromatography (petroleum ether : ethyl acetate = 1:0?9:1) to give the product of compound 88-b (1.07 g, yield: 60percent) as a colorless oil. 1H NMR (400 MHz, CHLOROFORM-d) delta=9.39 (br. s., 1H), 8.48 (s, 1H), 7.59 (d, J=8.53 Hz, 1H), 7.30 (s, 1H), 4.46 (q, J=7.03 Hz, 2H), 1.45 (t, J=7.15 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25 mg | With triethylamine; In chloroform; at 0 - 20℃; for 2.5h; | In a clean and dry 3000 mL round bottom flask, it was taken 400 mL of chloroform, 40 g of compound 8 and 38 g of triethylamine at room temperature under gentle stirring, then added 32 g of ethyl oxalyl chloride dropwise over a period of 0.5 h at 0-5 C. The reaction mass was maintained for 1 h at 0-5 C and another 1 h at room temperature until the reaction get complies in TLC. After completion of the reaction added 1N HCl (200 mL) to the wine red colour reaction mass to remove excess of triethylamine, the obtained organic residue after distillation under reduced pressure was isolated in isopropyl ether (IPE) and got 25 g pure material. 1H NMR (DMSO-d6): delta 12.21 (s, 1H),9.48 (s, 1H), 9.06 (t, 1H), 7.38 (t, 2H), 7.16 (t, 2H), 4.51 (d, 2H),3.36 (s, 3H), 1.64 (s, 6H); 13C NMR (DMSO-d6): delta 168.45, 162.53, 160.52, 160.12, 158.59, 156.92, 151.74, 145.72, 134.90,134.88, 129.47, 124.40, 115.25, 115.04, 62.19, 57.16, 41.65,32.96, 26.90, 13.78. Mass: M+: 434.42, M-H: 433.3 (-ve scan). |
Tags: 4755-77-5 synthesis path| 4755-77-5 SDS| 4755-77-5 COA| 4755-77-5 purity| 4755-77-5 application| 4755-77-5 NMR| 4755-77-5 COA| 4755-77-5 structure
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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 |
Sorry,this product has been discontinued.
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