Structure of 28489-45-4
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CAS No. : | 28489-45-4 |
Formula : | C6H6N2O3 |
M.W : | 154.12 |
SMILES Code : | CC1=NC(O)=CC=C1[N+]([O-])=O |
MDL No. : | MFCD00092010 |
InChI Key : | AJDDHNXZBGZBJN-UHFFFAOYSA-N |
Pubchem ID : | 543053 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
78.94 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.19 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.06 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.81 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.38 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.8 |
Solubility | 2.44 mg/ml ; 0.0158 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.31 |
Solubility | 0.757 mg/ml ; 0.00491 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.2 |
Solubility | 9.66 mg/ml ; 0.0627 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 |
-6.49 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) |
1.78 |
* 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 |
---|---|---|
78% | With phosphorus pentachloride; trichlorophosphate; at 150℃; for 2h; | Example 1153-((5-Amino-6-methylpyridin-2-yl)ethynyl)-7,7-dimethyl-7,8-dihydroquinoone[00319] A mixture of 6-methyl-5-nitropyridin-2-ol (500 mg, 3.24 mmol), POCI3 (0.5 mL) and PCI5 (200 mg) is stirred at 150 °C for 2 h, cooled to r.t, poured onto ice, and extracted with DCM (3x20 mL). The combined organic phases are washed with water to reach pH 7, dried over Na2S04 and concentrated at reduced pressure. The obtained residue is dried at reduced pressure to give 6-chloro-2-methyl-3-nitropyridine (430 mg, 78percent) as light brown solid.[00320]According to General Procedure 2, 3-ethynyl-7,7-dimethyl-7,8-dihydroquinolin- 5(6/-/)-one (199 mg, 1 .00 mmol) is reacted with 6-chloro-2-methyl-3-nitropyridine (172 mg, 1.00 mmol) in the presence of PdCI2(PPh3)2 (42 mg, 0.06 mmol), P(f-Bu)3 (16 mg, 0.08 mmol), and TEA (1 .5 mL) in DMF (3 mL) at 100 °C for 3 h. The crude product is purified by column chromatography (silica gel) to give the intermediate product 7,7- dimethyl-3-((6-methyl-5-nitropyridin-2-yl)ethynyl)-7,8-dihydroquinolin-5(6/-/)-one (80 mg, 16percent) as yellow solid.[00321 ]7,7-dimethyl-3-((6-methyl-5-nitropyridin-2-yl)ethynyl)-7,8-dihydroquinolin-5(6/-/)- one (194 mg, 0.58 mmol) is dissolved in EtOAc (10 mL) and cooled down to 0 °C. A solution of SnCl2*2H2O (650 mg, 2.90 mmol) in concentrated aqueous HCI solution (1 mL) is added dropwise. The reaction mixture is stirred at r.t. for 3 h, poured onto ice, treated with 15percent aqueous NaOH solution to reach pH 9-10, and extracted with EtOAc (3x25 mL). The combined organic phases are dried over Na2SO4 and concentrated at reduced pressure. The obtained residue is purified by preparative TLC (silica gel, DCM/EtOH, 40: 1 ) to provide the title compound (34 mg, 19percent).1H NMR (De-DMSO), deltaEta, 1 .05 (s, 6H), 2.29 (s, 3H), 2.59 (s, 2H), 3.03 (s, 2H), 5.51 (br s, 2H), 6.92 (d, 1 H), 7.24 (d, 1 H), 8.15 (s, 1 H), 8.83 (s, 1 H).LC/MS (M+H)+ = 306 |
63.8% | With phosphorus pentachloride; trichlorophosphate; at 100℃; for 2h; | The raw material 3 (150 mg) and PCl5(210 mg) and POCl3(180 mg) was placed in a round bottom flask and refluxed at 100 ° C for 2 h. The POCl was distilled off under reduced pressure3After stirring with water, the solid was precipitated and filtered under reduced pressure to give the crude product. Column chromatography gave pure product 4 (100 mg) in 63.8percent yield. |
62% | With phosphorus pentachloride; trichlorophosphate; In DMF (N,N-dimethyl-formamide); at 110 - 115℃; for 8h; | (c) To 6-Hydroxy-3-nitro-2-picoline (15.73 g, 0.102 mol) was added PCls (5.73 g, 0.027 mol) and POCh (2.9 ml, 0.032 mol). This mixture was heated at 110-115°C for 3 hrs. However, the amount of POCh added was only enough to moisten the starting material. More POC13 (3 ml) was added, the reaction mixture heated at 110-115°C but only sublination of PCls (100°C) was observed. DMF (5 ml) was added and the solution was heated at 115°C for 5 hrs, cooled and poured into a slush of ice and water. A beige product precipitated and the water suspension was stirred for 48 hrs. The brown precipitate was filtered off and washed with water. Purification by dry-flash dichloromethane yielded 10.93 g (62 percent) of 6-chloro-2-picoline. |
2.3 gm (85%) | With phosphorus pentachloride; trichlorophosphate; | 6-chloro-3-nitro-2-picoline A mixture of 2.42 gm (15.7 mMol) 6-hydroxy-3-nitro-2-picoline, 1.0 gm phosphorus pentachloride, and 0.5 mL phosphorus oxychloride was heated at 110° C. for 2.5 hours. The reaction mixture was cooled to room temperature and then an additional 0.5 gm of phosphorus pentachloride and 0.5 mL phosphorus oxychloride were added. Heating was resumed for one hour at which point the reaction mixture poured into 100 mL of an ice/water slurry. The resultant slurry is filtered and the solid dried under vacuum to provide 2.3 gm (85percent) of the desired compound as a brown solid. |
2.3 gm (85%) | With phosphorus pentachloride; trichlorophosphate; | 6-chloro-3-nitro-2-picoline A mixture of 2.42 gm (15.7 mMol) 6-hydroxy-3-nitro-2-picoline, 1.0 gm phosphorus pentachloride, and 0.5 mL phosphorus oxychloride was heated at 110°C for 2.5 hours. The reaction mixture was cooled to room temperature and then an additional 0.5 gm of phosphorus pentachloride and 0.5 mL phosphorus oxychloride were added. Heating was resumed for one hour at which point the reaction mixture poured into 100 mL of an ice/water slurry. The resultant slurry is filtered and the solid dried under vacuum to provide 2.3 gm (85percent) of the desired compound as a brown solid. |
Step 2 6-Chloro-2-methyl-3 -nitropyridineA roundbottom flask was charged with a solution of 6-methyl-5-nitropyridin-2-ol (1.5 g, 9.74 mmol) in phosphorus oxychloride (5 ml). To the mixture was added phosphoryl pentachloride (2.0 g, 9.59 mmol). The resulting solution was allowed to react, with stirring, for three hours while the temperature was maintained at reflux. The mixture was poured into ice water and the solids that formed were collected by filtration to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trichlorophosphate; at 115℃; for 3h; | A suspension OF 6-METHYL-5-NITRO-LH-PYRIDIN-2-ONE (Preparation 2,3. 53g, 22.9mmol) in phosphorous oxychloride (20mL) was heated to 115°C (oil bath temperature) for 3h then allowed to cool to rt. The phosphorous oxychloride was removed in vacuo and the residue poured into iced water (LOOML). The mixture was quenched by addition of saturated sodium bicarbonate solution, then the aqueous mixture was extracted with ethyl acetate (3 x 100ML). The combined organics were washed with brine, dried (MgSO4), filtered and concentrated III VACUO to furnish the title compound as a brown solid. 8N (CDCl3): 2.86 (3H, s), 7.36 (1H, d, 8.59Hz), 8.27 (1H, d, 8.32Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With trichlorophosphate; | Preparation 5 2-Chloro-5-Nitro-6-Methylpyridine A mixture of 2-oxo-5-nitro-6-methyl-1,2-dihydropyridine (38.95 g, 253 mmol), phosphorous oxychloride (12.3 mL, 130 mmol), and phosphorous pentachloride (27.9 g, 134 mmol) was heated at 110° C. for 2 hours, whereupon the reaction mixture was charged with an additional portion of phosphorous pentachloride and phosphorous oxychloride (9.9 g and 4.8 mL, respectively). The reaction was stirred 1 hour, then poured into ice-water (600 mL). The brown solid was filtered and washed with cold water, to give 40.88 g of the title compound (94percent). MS(m/e): 173 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In water; | A. 2-Hydroxy-5-nitro-6-methylpyridine To a suspension of a 2:1 mixture of 2-amino-5-nitro-6-methylpyridine and 2-amino-3-nitro-6-methylpyridine (2.5 g, 16.3 mmol) in 15 mL of water at 0 C. was added concentrated sulfuric acid (5 mL), followed by a solution of NaNO2 (2.25 g, 32.6 mmol) in 5 mL of water dropwise over 90 minutes. The solution was stirred 5 hours as it warmed to room temperature, cooled to 0 C. and filtered. The solid was washed with water (2*) and dried under vacuum to afford 1.84 g of a >4:1 mixture (by HPLC) of Compound A and <strong>[39745-39-6]2-hydroxy-3-nitro-6-methylpyridine</strong> (73%) as a tan solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | INTERMEDIATE 17 6-Methyl-5-nitro-2-(prop-2-yloxy)pyridine To a solution of 6-methyl-5-nitropyridin-2-ol (1.5 g, 9.7 mmol) in DMF (8 mL) was added CS2CO3 (6.2 g, 19 mmol) and the reaction mixture was stirred at room temperature for 15 minutes. <strong>[926-06-7]Isopropyl methanesulfonate</strong> (2.68 g, 19 mmol) was added and the reaction mixture was heated at 80°C for 2 h, then diluted with EtOAc (100 mL). The organic layer was washed with water, then separated, dried over Na2S04 and concentrated in vacuo. The residue was purified by silica gel (100:200 mesh) column chromatography, using 5percent EtOAc in hexane as eluent, to afford the title compound (1.2 g, 63percent). 5H (DMSO-d6) 8.33 (d, J 8.98 Hz, 1H), 6.79 (d, J 8.98 Hz, 1H), 5.37 (m, 1H), 2.70 (s, 3H), 1.11-1.38 (m, 6H). |
Tags: 28489-45-4 synthesis path| 28489-45-4 SDS| 28489-45-4 COA| 28489-45-4 purity| 28489-45-4 application| 28489-45-4 NMR| 28489-45-4 COA| 28489-45-4 structure
A750384 [6854-07-5]
5-Nitro-2-oxo-3-pyridinecarboxylic Acid
Similarity: 0.72
A358798 [149082-03-1]
(3,5-Dimethyl-4-nitropyridin-2-yl)methanol
Similarity: 0.62
A246001 [86454-13-9]
2-Hydroxy-6-methylisonicotinic acid
Similarity: 0.61
A196642 [5467-69-6]
6-Methoxy-2-methyl-3-nitropyridine
Similarity: 0.93
A109180 [6635-90-1]
2-Methoxy-4-methyl-5-nitropyridine
Similarity: 0.80
A196642 [5467-69-6]
6-Methoxy-2-methyl-3-nitropyridine
Similarity: 0.93
A109180 [6635-90-1]
2-Methoxy-4-methyl-5-nitropyridine
Similarity: 0.80
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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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