Structure of 5418-51-9
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CAS No. : | 5418-51-9 |
Formula : | C5H4N2O3 |
M.W : | 140.10 |
SMILES Code : | O=[N+](C1=CN=C(O)C=C1)[O-] |
MDL No. : | MFCD00006276 |
InChI Key : | XKWSQIMYNVLGBO-UHFFFAOYSA-N |
Pubchem ID : | 79453 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 35.08 |
TPSA ? Topological Polar Surface Area: Calculated from |
78.94 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.8 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.98 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.7 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.21 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.23 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.7 |
Solubility | 2.77 mg/ml ; 0.0198 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.23 |
Solubility | 0.833 mg/ml ; 0.00594 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.8 |
Solubility | 22.0 mg/ml ; 0.157 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 |
-6.46 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 |
1.0 |
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) |
1.76 |
* 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 |
---|---|---|
53% | With iodine; potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 15h; | Synthesis of 3-Iodo-5-nitro-pyridin-2-ol (CXXI): To a mixture of 2-Hydroxy-5-nitro pyridine (14 g, 99.9 mmol) and potassium carbonate (13.8 g, 99.9 mmol) in N,N- dimethylformamide (100 mL) was added iodine (25.3 g, 99.7 mmol) in a portionwise fashion at room temperature. The resulting reaction mixture was heated at 85 C for 15 h, before 5 being allowed to cool to room temperature. The progress of the reaction was monitored by TLC. The reaction mixture was diluted with water (150 mL) and then extracted with ethyl acetate (75 mL x 3). The combined organic extracts were washed with brine (150 mL x 3), dried over anhydrous sodium sulfate and concentrated in vacuo. The remaining solid residue was washed with n-hexanes (50 mL x 2) and allowed to dry in a stream of air to afford CXXI 10 (14 g, 53%) as a brown solid, which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium iodate; potassium iodide; In sulfuric acid; water; | A. 2-Hydroxy-3-iodo-5-nitropyridine (765A) 2-Hydroxy-5-nitropyridine (7.0 g, 50 mmol) was suspended in 100 mL of 20% sulfuric acid and then treated with potassium iodate (4.2 g, 19.6 mmol) dissolved in 10 mL of water. The mixture was heated to 100 C. and potassium iodide (8.0 g, 48.2 mmol) dissolved in 20 mL of water was added dropwise over one h. The reaction mixture turns a purplish-red and a precipitate forms. After 0.5 h, the reaction mixture is cooled and filtered. The solid is stirred for 15 min with 10% sodium meta-bisulfite solution, filtered, washed with water and dried at 80 C. overnight on a vacuum pump to give the desired compound 765A (12.32 g, 92%) as a yellow solid. The product was characterized by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.4% | With sodium carbonate; In acetonitrile; at 0 - 20℃; for 16.0h; | To a solution of 5-nitropyridin-2-ol (XCVIII) (1 g, 7.14 mmol) in acetonitrile (10 mL) at 0 C. was added sodium carbonate (1.513 g, 14.28 mmol), and 2,2-difluoro-2-(fluorosulfonyl)acetic acid (XCIX) (1.107 mL, 10.71 mmol). The reaction was allowed to stir from 0 C. to room temperature over 16 h. The reaction was quenched with saturated aqueous sodium bicarbonate and extracted with EtOAc, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified on a silica gel column (0%?10% EtOAc/hexane) to give 2-(difluoromethoxy)-5-nitropyridine (C) as a light brown oil (1.01 g, 5.31 mmol, 74.4% yield). 1H NMR (DMSO-d6, 500 MHz) delta ppm 7.36 (d, J=9.61 Hz, 1H), 7.82 (t, J=71.70 Hz, 1H), 8.70 (dd, J=9.06, 2.74 Hz, 1H), 9.15 (d, J=2.74 Hz, 1H); ESIMS found for C6H4F2N2O3 m/z 191.0 (M+H). |
49% | With sodium sulfate; In acetonitrile; at 20℃; for 16.0h; | Step A: 2-(Difluoromethoxy)-5-nitropyridine To 2-hydroxy-5-nitropyridine (7 g, 50 mmol) in acetonitrile (500 mL) was added sodium sulfate (1.5 g, 10.6 mmol), and 2,2-difluoro-2-(fluorosulfonyl)acetic acid (6.2 mL, 60 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The reaction was quenched with saturated aqueous sodium bicarbonate and the acetonitrile was removed in vacuo. The remaining aqueous component was extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The pale brown oily solid was triturated with ether/hexanes, filtered and the filtrate concentrated to afford 2-(difluoromethoxy)-5-nitropyridine (4.7 g, 24.7 mmol, 49% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) delta ppm 9.14 (d, J=2.76 Hz, 1H), 8.68 (dd, J=9.03, 2.76 Hz, 1H), 7.98 (s, 0.5H), 7.62 (s, 0.5H), 7.34 (d, J=9.03 Hz, 1H). |
49% | With sodium sulfate; In acetonitrile; at 20℃; for 16.0h; | Step A: 2-(Difluoromethoxy)-5-nitropyridineTo 2-hydroxy-5-nitropyridine (7 g, 50 mmol) in acetonitrile (500 niL) was added sodium sulfate (1.5 g, 10.6 mmol), and 2,2-difluoro-2-(fluorosulfonyl)acetic acid (6.2 mL, 60 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The reaction was quenched with saturated aqueous sodium bicarbonate and the acetonitrile was removed in vacuo. The remaining aqueous component was extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The pale brown oily solid was triturated withether/hexanes, filtered and the filtrate concentrated to afford 2-(difluoromethoxy)-5- nitropyridine (4.7 g, 24.7 mmol, 49 % yield) as a yellow oil. XH NMR (400 MHz, DMSO-de) delta ppm 9.14 (d, J=2.76 Hz, 1 H), 8.68 (dd, J=9.03, 2.76 Hz, 1 H), 7.98 (s, 0.5 H), 7.62 (s, 0.5 H), 7.34 (d, J=9.03 Hz, 1 H). |
49% | With sodium sulfate; In acetonitrile; at 20℃; for 16.0h; | To 2-hydroxy-5-nitropyridine (7 g, 50 mmol) inacetonitrile (500 mL) was added sodium sulfate (1.5 g, 10.6mmol), and 2,2-difluoro-2-(fluorosulfonyl)acetic acid (6.2ml., 60 mmol) and the reaction was allowed to stir at roomtemperature for 16 hours. The reaction was quenched withsaturated aqueous sodium bicarbonate and the acetonitrilewas removed in vacuo. The remaining aqueous componentwas extracted with ethyl acetate, washed with brine, driedover sodium sulfate, filtered and concentrated in vacuo. Thepale brown oily solid was triturated with ether/hexanes, filteredand the filtrate concentrated to afford 2-(difluoromethoxy)-5-nitropyridine (4.7 g, 24.7 mmol, 49% yield) asa yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.5%; 15% | In acetonitrile; for 48.0h;Reflux; | 2-Hydroxy-5-nitro-pyridine (5 g) was treated with sodium chlorodifluoro- acetate (11.5 g) in refluxing acetonitrile (186 ml) for 2 days. The solvent was evaporated, the residue poured into ethyl acetate, washed with brine, dried over sodium sulfate and then concentrated in vacuo. Chromatography on silica gel (eluent: hexane / ethyl acetate 1 :1) afforded 2-difluoromethoxy-5-nitro-pyridine (1 g, 15%) and l-difluoromethyl-5-nitro-lH- pyridin-2-one (90 mg, 1.5%). 2-Difluoromethoxy-5-nitro-pyridine: MS (ES+) 191 (MEta+); IH NMR (400 MHz, CDCl3) 7.05 (d, IH), 7.51 (t, IH), 8.53 (dd, IH), 9.09 (d, IH). 1-Difluoromethyl-5-nitro-lH-pyridin-2-one: MS (ES+) 191 (MEta+); 6.65 (d, IH), 7.63 (t, IH), 8.14 (dd, IH), 8.73 (d, IH). |
1.5%; 15% | In acetonitrile; for 48.0h;Reflux; | Step A: 2-Hydroxy-5-nitro-pyridine (5 g) was treated with sodium chlorodifluoro- acetate (1 1.5 g) in refluxing acetonitrile (186 ml) for 2 days. The solvent was evaporated, the residue poured into ethyl acetate, washed with brine, dried over sodium sulfate and then concentrated in vacuo. Chromatography on silica gel (eluent: hexane / ethyl acetate 1 :1) afforded 2-difluoromethoxy-5-nitro-pyridine (I g, 15%) and l-difluoromethyl-5-nitro-lH- pyridin-2-one (90 mg, 1.5%). 2-Difluoromethoxy-5-nitro-pyridine: MS (ES+) 191 (MH+); IH NMR (400 MHz, CDCl3) 7.05 (d, IH), 7.51 (t, IH), 8.53 (dd, IH), 9.09 (d, IH). 1-Difluoromethyl-5-nitro-l//-pyridin-2-one: MS (ES+) 191 (MH+); 6.65 (d, IH), 7.63 (t, IH), 8.14 (dd, IH), 8.73 (d, IH). |
In acetonitrile; for 48.0h;Reflux; | This example illustrates the preparation of 2-chloro-N-{r-[4-(5-chloro-pyrirnidin-2- yl)-benzyl]-6-difluoromethoxy- 1 ',2',3',4',5',6'-hexahydro-[2,4']bipyridinyl-3-yl} - isonicotinamide (Compound B6 of Table B).The title compound was obtained from 2-bromo-6-difluoromethoxy-pyridin-3-yl- amine following the procedures described in Example 5. 2-Bromo-6-difluoromethoxy-pyridin- 3-yl-amine was prepared as follows:Step A: 2-Hydroxy-5-nitro-pyridine (5 g) was treated with sodium chlorodifluoro- acetate (11.5 g) in refluxing acetonitrile (186 ml) for 2 days. The solvent was evaporated, the residue poured into ethyl acetate, washed with brine, dried over sodium sulfate and then concentrated in vacuo. Chromatography on silica gel (eluent: hexane / ethyl acetate 1 :1) afforded 2-difluoromethoxy-5-nitro-pyridine (1 g) and l-difluoromethyl-5-nitro-lH-pyridin-2- one (90 mg). 2-Difluoromethoxy-5-nitro-pyridine: MS (ES+) 191 (MH+); IH NMR (400 MHz, CDCl3) 7.05 (d, IH), 7.51 (t, IH), 8.53 (dd, IH), 9.09 (d, IH). l-Difluoromethyl-5- nitro-lH-pyridin-2-one: MS (ES+) 191 (MEta+); IH NMR (400 MHz, CDCl3) 6.65 (d, IH), 7.63 (t, IH), 8.14 (dd, IH), 8.73 (d, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; for 72.0h;Reflux; | Step-1 -Preparation of 2-(difluoromethoxy)-5-nitropyridine To a solution of 2-hydroxy-5-nitro pyridine (10 g, 0.071 mol) in acetonitrile (100 mL) was added sodium chlorodifluoroacetate (11.5 g, 0.075 mol). The reaction mass was refluxed for 72 h. The excess of solvent was removed under vacuum and the reaction mass was diluted with ethyl acetate and water. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated. The obtained crude was purified by column chromatography on neutral alumina eluting with 10% EtOAc: Pet.ether to afford 0.900 g of the desired product. 1HNMR (DMSO-d6): delta 7.05 (d, J=8.7 Hz, 1H), 7.53 (d, J=71.4 Hz, 1H), 8.54 (dd, J=8.1 Hz & 5.4 Hz, 1H), 7.91 (s, 1H); MS [M-]: 190.83. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With di-isopropyl azodicarboxylate; triphenylphosphine; In toluene; at 80℃; for 3h; | General procedure: To a stirred solution of 39 (0.100g, 0.433mmol), appropriate substituted phenol (0.649mmol) and PPh3 (0.182g, 0.693mmol) in anhydrous toluene (5mL) was added DIAD (0.14mL, 0.693mmol) at 80C. After 3h, EtOAc (40mL) was added to the resulting solution. The organic layer was washed with 0.5M aqueous NaOH (40mL) and water (2×40mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash silica gel column chromatography eluting with Hexanes/EtOAc (9:1) or (95:5). |
Tags: 5418-51-9 synthesis path| 5418-51-9 SDS| 5418-51-9 COA| 5418-51-9 purity| 5418-51-9 application| 5418-51-9 NMR| 5418-51-9 COA| 5418-51-9 structure
A774541 [161117-88-0]
tert-Butyl (5-nitropyridin-2-yl)carbamate
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tert-Butyl 4-(5-nitropyridin-2-yl)piperazine-1-carboxylate
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A191405 [21901-41-7]
2-Hydroxy-4-methyl-5-nitropyridine
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A191405 [21901-41-7]
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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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