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Structure of 99368-67-9
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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. : | 99368-67-9 |
Formula : | C6H2ClF3N2O2 |
M.W : | 226.54 |
SMILES Code : | FC(C1=CC([N+]([O-])=O)=CN=C1Cl)(F)F |
MDL No. : | MFCD00792435 |
InChI Key : | OPEZLLCPUDLUFV-UHFFFAOYSA-N |
Pubchem ID : | 3849140 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H301-H315-H318-H335 |
Precautionary Statements: | P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P330-P332+P313-P362-P403+P233-P405-P501 |
Class: | 8(6.1) |
UN#: | 2922 |
Packing Group: | Ⅲ |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.07 |
TPSA ? Topological Polar Surface Area: Calculated from |
58.71 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.53 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.81 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.98 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.97 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.9 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.02 |
Solubility | 0.215 mg/ml ; 0.000947 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.41 |
Solubility | 0.0882 mg/ml ; 0.00039 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.92 |
Solubility | 0.275 mg/ml ; 0.00121 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 |
Yes |
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) |
Yes |
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 |
-5.89 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 |
0.0 |
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 |
3.0 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) |
2.18 |
* 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 |
---|---|---|
80% | With ammonia In methanol at 20℃; for 14 h; | A solution of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (15 g, 66.2 mmol) and ammonia solution in MeOH (7 N, 150 mL, 1.05 mol) was stirred at room temperature for 14 h. After completion of the reaction, reaction mixture was concentrated under vacuum and residue was diluted with water (100 mL) and aqueous phase was extracted with ethyl acetate (100 mL x 3), combined organic layer was dried over anhydrous sodium sulphate and filtered. The filtrate was rotary evaporated to afford 11 g (80percent) of the titled product as yellow solid.1HNMR (400 MHz, DMSO- d6) U9.06 (d, J = 2.7 Hz, 1H), 8.40 (d, J = 2.7 Hz, 1H), 8.04 (s, 2H); ESI-MS (m/z) 208.33 (MH)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5-Nitro-3-(trifluoromethyl)pyridin-2(1H)-one was treated with thionyl chloride and then the resulting <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> was treated with dimethylamine to obtain N,N-dimethyl-5-nitro-3-(trifluoromethyl)pyridin-2-amine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With phosphorus pentachloride; trichlorophosphate; at 110 - 120℃; for 8.0h; | a mixture of 5-nitro-3- (trifluoromethyl) pyridine -2 (1H) -One, 3 (1.50g, 7.21mmol), POCl3 (2.76g, 18.02mmol) and PCl5(1.4g, 10. 09mmol) was heated 8 hours to about 110 ~ 120 and poured into ice water. Themixture was neutralized with solid NaHCO3, and extracted with ethylacetate (3 × 40ml). The organic phases were combined, dried over Na2SO4,all solvents were evaporated under reduced pressure to give 2-chloro-5-nitro-3-(trifluoromethyl) pyridine 4. |
96% | With phosphorus pentachloride; trichlorophosphate; at 110 - 120℃; for 8.0h; | Synthesis of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine, 4 (0076) (0077) A mixture of 5-nitro-3-(trifluoromethyl)pyridin-2(1H)-one 3 (1.50 g, 7.21 mmol), POCl3 (2.76 g, 18.02 mmol) and PCl5 (1.4 g, 10.09 mmol) is heated to about 110-120° C. for 8 hours and then poured into ice water. The mixture is neutralized with solid NaHCO3 and extracted with ethyl acetate (3×40 ml). The combined organic phases is dried over Na2SO4 and all solvents removed under reduced pressure to obtain 2-chloro-5-nitro-3-(trifluoromethyl)pyridine 4. |
With thionyl chloride; | 5-Nitro-3-(trifluoromethyl)pyridin-2(1H)-one was treated with thionyl chloride and then the resulting 2-chloro-5-nitro-3-(trifluoromethyl)pyridine was treated with dimethylamine to obtain N,N-dimethyl-5-nitro-3-(trifluoromethyl)pyridin-2-amine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In acetonitrile; for 1.0h;Heating / reflux; | C. To a solution of compound 26c (1.136 g, 5.01 mmol) in 50 mL CH3CN was added imidazole (0.514 g, 7.55 mmol) and iPr2NEt (1.75 mL, 10.0 mmol). The reaction was heated at reflux for 1 hour then concentrated in vacuo to a residue. The residue was purified via silica gel chromatography (40-80percent EtOAc/heptane) to give compound 26d as a waxy yellow solid. MS: M+H+=258, 1H NMR (d6-DMSO): delta 9.66 (s, 1H), 9.13 (s, 1H), 8.13 (s, 1H), 7.65 (s, 1H), 7.21 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With iron; ammonium chloride; In ethanol; water; at 80℃; for 4.0h; | To a solution of <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (10.0 g, 44.1 mmol) in ethanol:water:TH F tin (2:2:1, 150 mL) were added, NH4CI (16.53 g, 309 mmol) and iron powder (17.26 g, 309 mmol). The resulting reaction mixture was stirred at 80eC for 4 h. After completion of the reaction, the reaction mixture was cooled to room temprature, filtered over celite bed and filtrate bed was washed with ethyl acteate (200 mL). Combined filtrate was concentrated to afford 8.0 g (92%) of the titled product as a brown solid. 1HNMR (400 MHz, DMSO-d6) U7.93 (d, J = 2.7 Hz, 1H), 7.39 (d, J = 2.8 Hz, 1H), 6.02 (s, 2H); ESI-MS (m/z) 197.26 (MH)+. |
92% | With hydrogen;5 % platinum on carbon; zinc dibromide; In ethyl acetate; for 20.0h; | C. 6-Chloro-5-(trifluoromethyl)pyridin-3-amine A mixture of 2-chloro-5-nitro-3-(trifiuoromethyi)pyridine (5.25 rnrnoi, 1.1S g), ZnBr2 (1.05 mmol, 0.200 g) and 5% Pt (C) (1.58 mmol, 0.31 g) in ethyl acetate (50 ml) was stirred for 20 hours under hydrogen atmosphere. The catalyst was filtered off and the solid was washed with warmed ethanol. The solvent was evaporated affording the expected product (0.95 g, yield 92%). 1H NMR (300 MHz, DMSO-d6) delta ppm: 5.59 (bs, 1 H), 7.37 (s, 1 H), 7.92 (s, 1 H). C. 6-Chloro-5-(trifluoromethyl)pyridin-3-amine <n="71"/>A mixture of <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (5.25 mmol, 1.19 g), ZnBr2 (1.05 mmol, 0.200 g) and 5% Pt (1.58 mmol, 0.31 g) in ethyl acetate (50 ml) was stirred for 20 hours under hydrogen atmosphere. The catalyst was filtered off and the solid was washed with warmed ethanol. The solvent was evaporated affording the expected product (0.95 g, yield 92%). delta 1H NMR (300 MHz1 DMSO-d6): 5.59 (bs, 1 H)1 7.37 (s, 1 H), 7.92 (s, 1H). |
65% | With water; iron; ammonium chloride; In methanol; at 20℃; for 4.08333h; | Reference Example 119 6-chloro-5-(trifluoromethyl)pyridine-3-amine; Reduced iron (1.3 g) and ammonium chloride (2.1 g) were added to water (40 mL), and the mixture was stirred at room temperature for 5 min. A solution of <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (1.8 g) in methanol (40 mL) was added, and the mixture was stirred at room temperature for 1 hr. Reduced iron (2.3 g) was added, and the mixture was further stirred at the same temperature for 3 hr. The reaction mixture was filtered through celite, and celite was washed with ethyl acetate. The filtrate was extracted with ethyl acetate, and the extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1?1:1) to give the title compound as a solid (yield 1.0 g, 65%). 1H-NMR (CDCl3) delta: 7.29 (1H, m), 7.99 (1H, m), 2H not detected. |
51.9% | With iron; acetic acid; at 80℃; for 0.25h; | To a mixture of <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (2 g, 8.83 mmol) in acetic acid (10 mL) was added iron (2.465 g, 44.1 mmol) in one portion. The mixture was stirred at 80 C. for 15 min. The mixture was filtered and concentrated and then washed with aq. NaOH and extracted with EA. he crude material was purified by silica column chromatography (PE/EA=5:1). All fractions found to contain product by TLC (PE/EA=8:1, Rf=0.6) were combined and concentrated to yield a yellow solid of 6-chloro-5-(trifluoromethyl)pyridin-3-amine (1 g, 4.58 mmol, 51.9% yield): 1H NMR (400 MHz, CD3OD) delta 8.06 (s, 1H), 7.86 (d, J=8.60 Hz, 1H), 7.53 (d, J=8.60 Hz, 1H), 7.46-7.26 (m, 5H), 4.16-4.11 (m, 2H), 3.81 (s, 2H), 1.47 (t, J=6.62 Hz, 3H); ES-LCMS m/z 197.0 (M+H). |
51.9% | With iron; acetic acid; at 80℃; for 0.25h; | To a mixture of <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (2 g, 8.83 mmol) in acetic acid (10 inL) was added iron (2.465 g, 44.1 mmol) in one portion. The mixture was stirred at 80 C for 15 min. The mixture was filtered and concentrated and then washed with aqueous NaOH and extracted with EA. The crude material was purified by silica column chromatography (PE/EA = 5: 1). All fractions found to contain product by TLC (PE/EA = 8: 1, Rf = 0.6) were combined and concentrated to yield a yellow solid of 6-chloro-5-(trifluoromethyl)pyridin-3 -amine (1 g, 4.58 mmol, 51.9% yield): lH NMR (400 MHz, CD3OD) delta 8.06 (s, 1H), 7.86 (d, J = 8.60 Hz, 1H), 7.53 (d, J = 8.60 Hz, 1H), 7.46-7.26 (m, 5H), 4.16-4.11 (m, 2H), 3.81 (s, 2H), 1.47 (t, J = 6.62 Hz, 3H); ES-LCMS m/z 197.0 (M+H). |
51.9% | With iron; acetic acid; at 80℃; for 0.25h; | To a mixture of 2-chloro-5-nitro-3- (trifluoromethyl) pyridine (2 g 8.83 mmol) in AcOH (10 mL) was added iron (2.465 g 44.1 mmol) in one portion. The mixture was stirred at 80 for 15 min. The mixture was filtered and concentrated and then washed with aq. NaOH and extracted with EA. The residue was purified by silica column chromatography (PE/EA 51) . All fractions found to contain product by TLC (PE/EA 81 Rf 0.6) were combined and concentrated to yield a yellow solid of 6-chloro-5- (trifluoromethyl) pyridin-3-amine (1 g 4.58 mmol 51.9yield) 1HNMR(400 MHz CD3OD) delta 8.06 (s 1H) 7.86 (d J 8.60 Hz 1H) 7.53 (d J 8.60 Hz 1H) 7.46-7.26 (m 5H) 4.16-4.11 (m 2H) 3.81 (s 2H) 1.47 (t J 6.62 Hz 3H) ES-LCMS m/z 197.0 (M+H) |
With ethanol; water; iron; calcium chloride; for 1.0h;Heating / reflux; | 5. 6-Chloro-5-trifluorom.eihyl-pyridin-3-ylam.ine Heat a mixture of <strong>[99368-67-9]2-chloro-5-nitro-3-trifluoromethyl-pyridine</strong> (2.27 g, 10 mmol), calcium chloride (1.1 g, 10 mmol) and iron powder (4.5 g) in ethanol (30 mL) and water (5 mL) at reflux for 1 hour. Cool the mixture and filter through Celite. Evaporate the filtrate, dissolve the residue in EtOAc (200 mL) and wash with saturated NaHCO3(aq) (100 mL) and brine (100 mL). Dry the organic extract over MgSO4 and remove the solvent under reduced pressure to yield the title compound. | |
With ammonium chloride; zinc; In ethanol; water; for 18.0h; | EXAMPLE 27; N-[6-(3-Hydroxy-phenyl)-5-trifluoromethyl-pyridin-3-yl]-3-(4-trifluoromethyl-phenyl)-propionamide (Cpd 210) A. To a solution of compound 26c (1.478 g, 6.52 mmol) in 20 mL 4:1 EtOH/H2O was added NH4Cl (0.524 g, 9.80 mmol) and Zn powder (3.44 g, 52.6 mmol, <10 micron). The reaction was stirred under a nitrogen atmosphere for 18 hours then partitioned between 75 mL EtOAc and 75 mL H2O. This solvent mixture was filtered over a pad of Celite, 50 mL brine was added to help with the emulsion. The mixture was filtered again over Celite. The organic phase was isolated and dried over Na2SO4, filtered, and evaporated in vacuo to a residue. The residue was purified via silica gel chromatography (30-60% EtOAc/heptane) to give compound 27a as a yellow-orange powder. MS: M+H+=197.0, 1H NMR (d6-DMSO): delta 7.93 (d, 1H), 7.39 (d, 1H), 6.02 (s, 2H). | |
With Raney-Ni; In tetrahydrofuran; for 24.0h; | 2-chloro-5-nitro-3-(trifluoromethyl) pyridine 4 (1.57g, 6.93mmol) was dissolved in tetrahydrofuran(THF) (10 ml), then was added to THF (20 ml) suspension of Raney -Ni (200 mg).Hydrogen gas was gentle foaming passing through a 24 hour stirring solutionusing a balloon. The mixture was filtered throughCelite (registered trademark) (World Minerals Inc., Lompoc, CA) and the solventwas evaporated under reduced pressure to obtain 6-chloro-5- (trifluoromethyl)pyridin-3-amine 5. | |
With hydrogen; In tetrahydrofuran; at 22℃; for 24.0h; | Synthesis of 6-chloro-5-(trifluoromethyl)pyridin-3-amine, 5 (0078) (0079) <strong>[99368-67-9]2-Chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> 4 (1.57 g, 6.93 mmol) is dissolved in tetrahydrofuran (THF) (10 ml) and added to a suspension of Raney-Ni (200 mg) in THF (20 ml). Hydrogen gas is slowly bubbled through the stirred solution for 24 hours using a balloon. The mixture is filtered through Celite (available from World Minerals, Inc., Lompoc, Calif.) and the solvent is removed under reduced pressure to obtain 6-chloro-5-(trifluoromethyl)pyridin-3-amine 5. | |
With iron; ammonium chloride; In methanol; water; at 20℃; for 4.0h; | (0875) A mixture of iron (1.5 g) and ammonium chloride (2.38 g) in water (40 ml) was stirred at room temperature for 5 minutes. To this suspension was added Compound 288B in methanol (40 ml). The reaction mixture was stirred at room temperature for 1 hour. More iron (1.8 g) was added to the reaction mixture, and it was stirred for another 3 hours. The solid from the reaction mixture was filtered off, and the filtrate was partitioned between water and ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with 20percent ethyl acetate in hexanes to provide the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With thionyl chloride; In N,N-dimethyl-formamide; at 100℃; for 10.0h; | SOCl2 (18.45 mL, 253 mmol) was added to a solution of <strong>[99368-66-8]5-nitro-3-(trifluoromethyl)pyridin-2-ol</strong> (2.63 g, 12.64 mmol). DMF (1.957 mL, 25.3 mmol) was added and the mixture was at 100 C. for 10 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The resulting 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (2.46 g, 10.86 mmol, 86% yield) was used in the next step without further purification. TLC (PE/EA=5:1, Rf=0.6): 1H NMR (400 MHz, CDCl3) delta: 9.23-9.59 (m, 1H), 8.79 (d, J=2.4 Hz, 1H). |
86% | With thionyl chloride; N,N-dimethyl-formamide; at 100℃; for 10.0h; | SOCl2 (18.45 mL, 253 mmol) was added to a solution of 5 -nitro-3 -(trifluoromethyl)pyridin-2-ol (2.63 g, 12.64 mmol). DMF (1.957 mL, 25.3 mmol) was added and the mixture was at 100 C for 10 h. Then the solution was concentrated and distributed between EA and saturated NaHCC>3 solution. The combined organic extract was washed with brine, dried over MgSO/i, filtered and concentrated. The resulting 2-chloro-5 -nitro-3 -(trifluoromethyl)pyridine (2.46 g, 10.86 mmol, 86% yield) was used in the next step without further purification. TLC (PE/EA = 5: 1, Rf = 0.6): 'HNMR (400 MHz, CDCI3) delta: 9.23-9.59 (m, 1H), 8.79 (d, J = 2.4 Hz, 1H). |
77% | With phosphorus pentachloride; trichlorophosphate; at 90℃; for 3.0h; | Reference Example 118 2-chloro-5-nitro-3-(trifluoromethyl)pyridine; A mixture of <strong>[99368-66-8]5-nitro-3-(trifluoromethyl)pyridin-2-ol</strong> (2.65 g), phosphorus pentachloride (3.17 g) and phosphorus oxychloride (1.5 mL) was stirred at 90 C. for 3 hr. After cooling to room temperature, the reaction mixture was poured into ice, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1?3:1) to give the title compound as a yellow oil (yield 2.21 g, 77%). 1H-NMR (CDCl3) delta: 8.79-8.81 (1H, m), 9.40-9.41 (1H, m). |
55.1% | With thionyl chloride; N,N-dimethyl-formamide; at 80℃; for 16.0h; | To a mixture of 5-nitro-3- (trifluoromethyl) pyridin-2-ol (2 g 9.61 mmol) was added SOCl2(21.04 mL 288 mmol) and DMF (0.074 mL 0.961 mmol) . Then the mixture was stirred at 80 for 16 h. The mixture was concentrated and extracted with EA (2 x 100 mL) and washed with H2O (100 mL) to give the organic layer. The combined organic extract was washed with brine dried over Na2SO4 concentrated to yield a brown solid of 2-chloro-5-nitro-3- (trifluoromethyl) pyridine (2 g 5.30 mmol 55.1yield) 1HNMR(400 MHz CD3OD) delta 8.91 (d J 2.43 Hz 1H) 9.42 (d J 2.43 Hz 1H) |
With trichlorophosphate; at 85℃; for 18.0h; | 4. 2-ChlotauO-5-nitro-3-trifluoromethyl-pyridine Heat a mixture of <strong>[99368-66-8]5-nitro-3-trifluoromethyl-pyridin-2-ol</strong> (416 mg, 2.0 mmol) and phosphorus oxychloride (1 mL) at 85C for 18 hours. Cool the mixture and remove the volatiles by rotary evaporation. Dissolve the residue in EtOAc (15 mL) and wash with water (10 mL), saturatedNaHCO3(aq) (10 mL) and brine (10 mL). Dry the organic extract over MgSO4 and remove the solvent under reduced pressure to yield the title compound. | |
With thionyl chloride; In N,N-dimethyl-formamide; for 4.0h;Heating / reflux; | B. To a mixture of compound 26b (3.84 g, 18.5 mmol) in 20 mL SOCl2 was added 0.5 mL DMF. The mixture was heated to reflux for 4 hours then concentrated in vacuo. The residue was dissolved in benzene and concentrated again in vacuo. This residue was taken up in 50 mL EtOAc and washed with 50 mL saturated NaHCO3, and 50 mL brine, then dried over Na2SO4, and filtered and concentrated in vacuo. The resulting residue was chromatographed over silica gel (0-10% EtOAc/heptane) to give compound 26c as a pale yellow oil. 1H NMR (d6-DMSO): delta 9.52 (s, 1H), 8.92 (s, 1H). | |
With phosphorus pentachloride; trichlorophosphate; at 90℃; for 3.0h; | (0874) A mixture of Compound 288A (1.69 g), phosphorus pentachloride (2.03 g), and phosphoryl trichloride (0.97 ml) was heated at 90° C. for 3 hours. After cooling, the reaction mixture was poured into ice, and extracted with ethyl acetate three times. The extract was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with 10percent ethyl acetate in hexanes to provide the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; | Preparation 146 A mixture of <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (226mg) and 2-pyridylmethanamine (0.2ml) in tetrahydrofuran (2.0ml) was stirred for 18 hours. The mixture was poured into water and stirred for 1 hour. The precipitated solid was collected by filtration, washed with water, and dried to give 5-nitro-N-(2-pyridylmethyl)-3-(trifluoromethyl)-2-pyridinamine (277mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A. 2-Chloro-5-nitro-3-trifluoromethylpyridine (766A) 2-Chloro-3-iodo-5-nitropyridine (1.0 g, 3.5 mmol), methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.35 g, 1.82 mmol), and copper iodide (0.083 g, 0.44 mmol) were reacted in DMF (10 mL) according to the method described in example 763D. The crude product was purified by silica gel chomatography using 30percent CH2Cl2/hexane as the eluent to give compound 766A (0.278 g, 35percent) as a colorless oil. The product was characterized by 1H NMR and 19F NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
B. 5-Amino-2-chloro-3-trifluoromethylpyridine (766B) <strong>[99368-67-9]2-Chloro-5-nitro-3-trifluoromethylpyridine</strong> (0.16 g, 0.68 mmol) and iron powder (0.2 g, 3.42 mmol, 325 Mesh) were reacted as described in example 762D. Purification of the crude product by Prep-TLC using 10percent ether/CH2Cl2 as eluent gave compound 766B (0.098 g, 73percent) as a yellow solid. HPLC: 89percent at 2.52 min(YMC S5 ODS column) eluding with 10-90percent aqueous methanol containing 0.2percent phosphoric acid over a 4 min gradient monitoring at 220 nm. MS(ES): m/z 197.01 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); In N,N-dimethyl-formamide; at 130℃; for 0.333333h;Microwave irradiation; | l-cyano-S-nitro-S-trifluoromethylpyridine muwave 130 0C, 20 min[0066] Zinc cyanide (25 mg, 0.216 mmol, 1.2 eq) is added to the chloride (43 mg,0.180 mmol) solubilized in DMF (1 ml). The solution is degassed for 10 minutes. Then the ligand dppf (20 mg, 0.036 mmol, 0.2 eq) is added. The solution is degassed again for 5 min. The catalyst Pd2(dba)3 (25 mg, 0.027 mmol, 0.15 eq) is added, the solution is degassed for 5 more minutes. The reaction mixture is then heated at 130 0C for 20 min in a microwave. After filtration, the solvent is evaporated and the crude residue is purified by flash chromatography on silica gel (hexane /EtOAc) to afford 16 mg (40percent) of the desired product. [0067] 1H NMR (400 MHz, CDCl3) delta 8.60 (d, J= 2.5, IH); 9.08 (d, J= 2.5, IH), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With copper(l) iodide; In N,N-dimethyl-formamide; at 70℃; for 19.0h; | B. 2-Chloro-5-nitro-3-(trifluoromethyl)pyridineIn a schlenck tube, a mixture of <strong>[25391-60-0]2-chloro-3-iodo-5-nitropyridine</strong> (17.58 mmol, 5.00 g), methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (8.79 mmol, 1.12 ml) and CuI (2.64 mmol, 0.5 g) in DMF (30 ml) was heated at 7O0C for 3 hours under argon atmosphere. Methyl 2,2- difluoro-2-(fluorosulfonyl)acetate (4.40 mmol, 0.6 ml) was added and the mixture was heated at 7O0C for 16 hours. The solvent was evaporated and the crude mixture was extracted between ethyl acetate and water. The crude mixture was purified by chromatography over SiO2 eluting with hexane/DCM mixtures affording 1.19 g (yield 30percent) of the expected product.1H NMR (300 MHz, CDCI3) delta ppm: 8.82 (s, 1 H), 9.41 (s, 1 H). B. 2-ChIoro-5-nitro-3-(trifluoromethyl)pyridineIn a schlenk tube, a mixture of <strong>[25391-60-0]2-chloro-3-iodo-5-nitropyridine</strong> (17.58 mmol, 5.00 g), methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (8.79 mmol, 1.12 ml) and CuI (2.64 mmol, 0.5 g) in DMF (30 ml) was heated at 7O0C for 3 hours under argon atmosphere. Methyl 2,2- difluoro-2-(fluorosulfonyl)acetate (4.40 mmol, 0.6 ml) was added and the mixture was heated at 7O0C for 16 hours. The solvent was evaporated and the crude mixture was extracted between ethyl acetate and water. The crude mixture was purified by chromatography over SiO2 eluting with hexane/DCM mixtures affording 1.19 g (yield 30percent) of the expected product. delta 1H NMR (300 MHz, CDCI3): 8.82 (s, 1H), 9.41 (s, 1 H). |
21% | With copper(l) iodide; hydrogen; In N,N-dimethyl-formamide; at 70℃; for 19.0h; | In a 100 mL round bottom flask, a mixture of <strong>[25391-60-0]2-chloro-3-iodo-5-nitropyridine</strong> (250 mg, 0.88 mmol), methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.06 mL, 0.44 mmol) and Copper(l) iodide (25 mg, 0.13 mmol) in dimethylformamide was heated at 70 °C for 3h under hydrogen atmosphere. Another 0.03 mL methyl 2,2-difluoro-2-(fluorosulfonyl)acetate was added and the mixture was heated at 70 °C for 16 h. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure to afford the crude which was purified by column chromatography to give 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (41 mg, 21 percent). |
21% | With copper(l) iodide; hydrogen; In N,N-dimethyl-formamide; at 70℃; for 19.0h; | In a 100 mL round bottom flask, a mixture of <strong>[25391-60-0]2-chloro-3-iodo-5-nitropyridine</strong> (250 mg, 0.88 mmol), methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.06 mL, 0.44 mmol) and Copper(l) iodide (25 mg, 0.13 mmol) in dimethylformamide was heated at 70 °C for 3 h under hydrogen atmosphere. Another 0.03 mL methyl 2,2-difluoro-2-(fluorosulfonyl)acetate was added and the mixture was heated at 70 °C for 16 h. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure to afford the crude which was purified by column chromatography to give 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (41 mg, 21 percent). |
21% | With copper(l) iodide; hydrogen; In N,N-dimethyl-formamide; at 70℃; for 18.0h; | Step 1: In a 100 mL round bottom flask, a mixture of <strong>[25391-60-0]2-chloro-3-iodo-5-nitropyridine</strong> (250 mg, 0.88 mmol), methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.06 mL, 0.44 mmol) and Copper(I) iodide (25 mg, 0.13 mmol) in dimethylformamide was heated at 70° C. for 3 h under hydrogen atmosphere. Another 0.03 mL methyl 2,2-difluoro-2-(fluorosulfonyl)acetate was added and the mixture was heated at 70° C. for 16 h. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure to afford the crude which was purified by column chromatography to give 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (41 mg, 21percent). |
21% | With copper(l) iodide; In N,N-dimethyl-formamide; at 70℃; for 19.0h; | Step 1 In a 100 mL round bottom flask, a mixture of <strong>[25391-60-0]2-chloro-3-iodo-5-nitropyridine</strong> (250 mg, 0.88 mmol), methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.06 mL, 0.44 mmol) and Copper(I) iodide (25 mg, 0.13 mmol) in dimethylformamide was heated at 70° C. for 3 h under hydrogen atmosphere. Another 0.03 mL methyl 2,2-difluoro-2-(fluorosulfonyl)acetate was added and the mixture was heated at 70° C. for 16 h. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure to afford the crude which was purified by column chromatography to give 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (41 mg, 21percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;palladium 10% on activated carbon; In methanol; under 760.051 Torr; for 3.0h; | Example 10: 5-Trifluoromethyl-pyridin-3-ylamine.; A mixture of <strong>[99368-67-9]2-chloro-5-nitro-3-trifluoromethyl-pyridine</strong> (30 mg, 0.13 mmol), 10percent Pd/C (3 mg, 10percent w/w), and MeOH (5 mL) is stirred under 1 arm of hydrogen for 3 h. The mixture is then filtered over Celite.(R). and concentrated in vacuo to give the title compound as an oil. MS (ESI) m/z 162.9 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With 18-crown-6 ether; potassium carbonate; In acetonitrile; for 12.0h;Reflux; | <strong>[99368-67-9]2-Chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (41 mg, 0.18 mmol), dimethylamine hydrochloride (18 mg, 0.22 mmol), potassium carbonate (88 mg, 0.63 mmol) and 1 ,4,7, 10,13, 16-hexaoxacyclooctadecane (10 mg) was dissolved in acetonitrile. The reaction mixture was refluxed for 12 h. The reaction mixture was cooled to room temperature and then was concentrated under reduced pressure. Then the mixture was extracted with ethyl acetate and washed with water. The organic layer was concentrated under reduced pressure. The crude was purified by column chromatography to give N,N-dimethyl-5-nitro-3- (trifluoromethyl)pyridin-2-amine (36 mg, 84 percent). |
84% | With 18-crown-6 ether; potassium carbonate; In acetonitrile; for 12.0h;Reflux; | <strong>[99368-67-9]2-Chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (41 mg, 0.18 mmol), dimethylamine hydrochloride (18 mg, 0.22 mmol), potassium carbonate (88 mg, 0.63 mmol) and 1 ,4,7,10, 13, 16-hexaoxacyclooctadecane (10 mg) was dissolved in acetonitrile. The reaction mixture was refluxed for 12 h. The reaction mixture was cooled to room temperature and then was concentrated under reduced pressure. Then the mixture was extracted with ethyl acetate and washed with water. The organic layer was concentrated under reduced pressure. The crude was purified by column chromatography to give N,N-dimethyl-5-nitro-3- (trifluoromethyl)pyridin-2-amine (36 mg, 84 percent). |
84% | With 18-crown-6 ether; potassium carbonate; In acetonitrile; for 12.0h;Reflux; | Step 2: <strong>[99368-67-9]2-Chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (41 mg, 0.18 mmol), dimethylamine hydrochloride (18 mg, 0.22 mmol), potassium carbonate (88 mg, 0.63 mmol) and 1,4,7,10,13,16-hexaoxacyclooctadecane (10 mg) was dissolved in acetonitrile. The reaction mixture was refluxed for 12 h. The reaction mixture was cooled to room temperature and then was concentrated under reduced pressure. Then the mixture was extracted with ethyl acetate and washed with water. The organic layer was concentrated under reduced pressure. The crude was purified by column chromatography to give N,N-dimethyl-5-nitro-3-(trifluoromethyl)pyridin-2-amine (36 mg, 84percent). |
84% | With 18-crown-6 ether; potassium carbonate; In acetonitrile; for 12.0h;Reflux; | Step 2 <strong>[99368-67-9]2-Chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (41 mg, 0.18 mmol), dimethylamine hydrochloride (18 mg, 0.22 mmol), potassium carbonate (88 mg, 0.63 mmol) and 1,4,7,10,13,16-hexaoxacyclooctadecane (10 mg) was dissolved in acetonitrile. The reaction mixture was refluxed for 12 h. The reaction mixture was cooled to room temperature and then was concentrated under reduced pressure. Then the mixture was extracted with ethyl acetate and washed with water. The organic layer was concentrated under reduced pressure. The crude was purified by column chromatography to give N,N-dimethyl-5-nitro-3-(trifluoromethyl)pyridin-2-amine (36 mg, 84percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate; In tetrahydrofuran; at 50℃; for 10.0h; | To a solution of tert-butyl 2-cyanoacetate (523 mg, 3.71 mmol) in THF (15 mL) was added K2CO3 (854 mg, 6.18 mmol). Then <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (700 mg, 3.09 mmol) was added into the mixture and the mixture was at 50° C. for 10 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by preparative TLC (DCM/MeOH=20:1, Rf=0.4) to yield a light yellow solid of tert-butyl 2-cyano-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetate (1 g, 3.02 mmol, 98.0percent yield): 1H NMR (400 MHz, CD3OD) delta 8.99 (d, J=2.43 Hz, 1H), 8.36 (d, J=2.43 Hz, 1H), 3.35 (s, 1H), 1.49 (d, J=1.54 Hz, 9H); ES-LCMS m/z 276 (M-55). |
98% | With potassium carbonate; In tetrahydrofuran; at 50℃; for 10.0h; | To a solution of tert-butyl 2-cyanoacetate (523 mg, 3.71 mmol) in THF (15 mL) was added K2CO3 (854 mg, 6.18 mmol). Then <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (700 mg, 3.09 mmol) was added into the mixture and the mixture was at 50 °C for 10 h. Then the solution was concentrated and distributed between EA and saturated NaHC03 solution. The combined organic extract was washed with brine, dried over MgSO/i, filtered and concentrated. The crude material was purified by preparative TLC (DCM/MeOH = 20: 1, Rf = 0.4) to yield a light yellow solid of tert-butyl 2-cyano-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetate (1 g, 3.02 mmol, 98.0percent yield): lH NMR (400 MHz, CD3OD) delta 8.99 (d, J = 2.43 Hz, 1H), 8.36 (d, J = 2.43 Hz, 1H), 3.35 (s, 1H), 1.49 (d, J = 1.54 Hz, 9H); ES-LCMS m/z 276 (M-55). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 5.0h; | To a solution of <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (0.5, 2.207 mmol) and 2-(dimethylamino)ethanol (0.393 g, 4.41 mmol) in THF (10 mL) was added NaH (0.177 g, 4.41 mmol) at 0° C. The resulting mixture was stirred at rt. After 5 h, TLC analysis showed the starting material had disappeared. The solvent was removed in vacuo. The residue was dissolved in DCM (60 mL) and washed with H2O (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by silica column chromatography (DCM/MeOH=20/1) to yield a white solid of N,N-dimethyl-2-((5-nitro-3-(trifluoromethyl)pyridin-2-yl)oxy)ethanamine (0.5 g, 1.717 mmol, 78.0percent yield): 1H NMR (400 MHz, CD3OD) delta 9.25 (d, J=2.4 Hz, 1H), 8.74 (d, J=2.4 Hz, 1H), 4.73 (t, J=5.4 Hz, 2H), 2.88 (t, J=5.4 Hz, 2H), 2.37 (s, 6H); ES-LCMS m/z 280.0 (M+H). |
78% | With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 5.0h; | To a solution of 2-chloro-5 -nitro-3 -(trifluoromethyl)pyridine (0.5 , 2.207 mmol) and 2- (dimethylamino)ethanol (0.393 g, 4.41 mmol) in THF (10 mL) was added NaH (0.177 g, 4.41 mmol) at 0 °C. The resulting mixture was stirred at rt. After 5 h, TLC analysis showed the starting material had disappeared. The solvent was removed in vacuo. The residue was dissolved in DCM (60 mL) and washed with H20 (20 mL) and brine (20 mL). The organic layer was dried over NaaSOzi, filtered and concentrated. The crude product was purified by silica column chromatography (DCM/ Me OH = 20/1) to yield a white solid of N,N-dimethyl-2-((5 -nitro-3 - (trifluoromethyl)pyridin-2-yl)oxy)ethanamine (0.5 g, 1.717 mmol, 78.0percent yield): NMR (400 MHz, CD3OD) delta 9.25 (d, J = 2.4 Hz, 1H), 8.74 (d, J = 2.4 Hz, 1H), 4.73 (t, J = 5.4 Hz, 2H), 2.88 (t, J= 5.4 Hz, 2H), 2.37 (s, 6H); ES-LCMS m/z 280.0 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20.7% | With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 16.5h; | To a mixture of <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (500 mg, 2.207 mmol) in THF (10 mL) was added ethanol (0.155 mL, 2.65 mmol) and NaH (132 mg, 3.31 mmol). Then the mixture was stirred at 0° C. for 30 min, then warmed to rt and stirred for 16 h. The mixture was added to H2O and extracted with EA (2*50 mL) to give the organic layer. The combined organic extract was washed with brine, dried over Na2SO4 and concentrated to yield a brown oil of 2-ethoxy-5-nitro-3-(trifluoromethyl)pyridine (120 mg, 0.457 mmol, 20.7percent yield): 1H NMR (400 MHz, CD3OD) delta 9.27 (d, J=2.5 Hz, 1H), 8.75 (d, J=2.5 Hz, 1H), 4.67 (m, 2H), 1.47 (t, J=7.0 Hz, 3H). |
20.7% | With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 16.5h; | To a mixture of <strong>[99368-67-9]2-chloro-5-nitro-3-(trifluoromethyl)pyridine</strong> (500 mg, 2.207 mmol) in THF (10 mL) was added EtOH (0.155 mL, 2.65 mmol) and NaH (132 mg, 3.31 mmol). Then the mixture was stirred at 0 °C for 30 min, then warmed to rt and stirred for 16 h. The mixture was added to H20 and extracted with EA (2 x 50 mL) to give the organic layer. The combined organic extract was washed with brine, dried over NaaSOzi, filtered, and concentrated to yield a brown oil of 2- ethoxy-5-nitro-3-(trifluoromethyl)pyridine (120 mg, 0.457 mmol, 20.7percent yield): lH NMR (400 MHz, CD3OD) delta 9.27 (d, J = 2.5 Hz, 1H), 8.75 (d, J = 2.5 Hz, 1H), 4.67 (m, 2H), 1.47 (t, J = 7.0 Hz, 3H). |
With sodium hydride; at 0 - 85℃; for 2.0h; | At 0°C, NaH (141 mg, 3.53 mmol, 2.0 equiv) is added to 2-chloro-5-nitro-3- (trifluoromethyl)pyridine (400 mg, 1.77 mmol, 1.0 equiv) in ethanol (6 mL, 0.3 M), the resulting mixture is stirred at 85°C for 2 h. The mixture is diluted with DCM and water. The aqueous phase is extracted with DCM. The combined organic phase is filtered through a phase separator and concentrated under vacuum to afford the desired compound |
Tags: 99368-67-9 synthesis path| 99368-67-9 SDS| 99368-67-9 COA| 99368-67-9 purity| 99368-67-9 application| 99368-67-9 NMR| 99368-67-9 COA| 99368-67-9 structure
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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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