Structure of 1214336-90-9
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CAS No. : | 1214336-90-9 |
Formula : | C6H2BrF3N2O2 |
M.W : | 270.99 |
SMILES Code : | [O-][N+](=O)C1=CC(=CN=C1Br)C(F)(F)F |
MDL No. : | MFCD14702306 |
InChI Key : | MJTPNVWLMZFFIU-UHFFFAOYSA-N |
Pubchem ID : | 46315200 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 | 45.76 |
TPSA ? Topological Polar Surface Area: Calculated from |
58.71 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.22 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.59 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.92 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.01 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.14 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.34 |
Solubility | 0.125 mg/ml ; 0.00046 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.47 |
Solubility | 0.0915 mg/ml ; 0.000337 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.14 |
Solubility | 0.195 mg/ml ; 0.000718 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 |
-6.11 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.26 |
* 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 |
---|---|---|
Intermediate A1: 2-Bromo-3-nitro-5-trifluoromethyl-pyridine3-Nitro-5-(trifluoromethyl)pyridin-2-ol (31.00 g, 149 mmol) was dissolved in acetonitrile (250 ml) to give a dark brown solution. Phosphorus(V) oxybromide (85 g, 298 mmol) was added and the mixture was heated at reflux for 4.5 hours and then stirred at RT overnight. The reaction mixture was quenched by pouring into vigorously stirring water (600 ml) containing sodium hydrogencarbonate (110 g). The dark brown mixture was extracted with DCM (3×200 ml) and the organic phase was washed with water (200 ml) and brine (100 ml), dried (MgSO4) and concentrated in vacuo to afford the title product as a brown oil. 1H-NMR: [400 MHz, CDCl3, deltaH, 8.87 (1H, d, J=1.4 Hz, ArH), 8.39 (1H, d, J=1.9 Hz, ArH). | ||
With phosphorus(V) oxybromide; In acetonitrile; at 20.0℃;Reflux; | 3-Nitro-5-(trifluoromethyl)pyridin-2-ol (31.00 g, 149 mmol) was dissolved in acetonitrile (250 ml) to give a dark brown solution. Phosphorus(V) oxybromide (85 g, 298 mmol) was added and the mixture was heated at reflux for 4 hours and then stirred at RT overnight. The reaction mixture was quenched by pouring into vigorously stirring water (600 ml) containing sodium hydrogencarbonate (1 10 g). The dark brown mixture was extracted with DCM (3 x 200 ml) and the organic phase was washed with water (200 ml) and brine (100ml), dried (MgS04) and concentrated in vacuo to afford the title product as a brown oil. H-NMR: [400MHz, CDCI3, ? 8.87 (1 H, d, J = 1.4Hz, ArH), 8.39 (1 H, d, J = 1.9Hz, ArH). | |
With phosphorus(V) oxybromide; In acetonitrile; at 20.0℃;Reflux; | 3-Nitro-5-(trifluoromethyl)pyridin-2-ol (31.00 g, 149 mmol) was dissolved in acetonitrile (250 ml) to give a dark brown solution. Phosphorus(V) oxybromide (85 g, 298 mmol) was added and the mixture was heated at reflux for 4 hours and then stirred at RT overnight. The reaction mixture was quenched by pouring into vigorously stirring water (600 ml) containing sodium hydrogencarbonate (1 10 g). The dark brown mixture was extracted with DCM (3 x 200 ml) and the organic phase was washed with water (200 ml) and brine (100ml), dried (MgS04) and concentrated under reduced pressure to afford the title product as a brown oil. H-NMR: [400MHz, CDCI3, ? 8.87 (1 H, d, J = 1.4Hz, ArH), 8.39 (1 H, d, J = 1 .9Hz, ArH). |
With phosphorus(V) oxybromide; In acetonitrile; at 20.0℃;Reflux; | 3-Nitro-5-(trifluoromethyl)pyridin-2-ol (31.00 g, 149 mmol) was dissolved in acetonitrile (250 ml) to give a dark brown solution. Phosphorus(V) oxybromide (85 g, 298 mmol) was added and the mixture was heated at reflux for 4 hours and then stirred at RT overnight. The reaction mixture was quenched by pouring into vigorously stirring water (600 ml) containing sodium hydrogencarbonate (1 10 g). The dark brown mixture was extracted with DCM (3 x 200 ml) and the organic phase was washed with water (200 ml) and brine (100ml), dried (MgS04) and concentrated under reduced pressure to afford the title product as a brown oil. H-NMR: [400MHz, CDCI3, ? 8.87 (1 H, d, J = 1.4Hz, ArH), 8.39 (1 H, d, J = 1 .9Hz, ArH). | |
With phosphorus(V) oxybromide; at 20.0℃;Reflux; | 3-Nitro-5-(trifluoromethyl)pyridin-2-ol (31.00 g, 149 mmol) was dissolved in acetonitrile (250 ml) to give a dark brown solution. Phosphorus(V) oxybromide (85 g, 298 mmol) was added and the mixture was heated at reflux for 4 hours and then stirred at RT overnight. The reaction mixture was quenched by pouring into vigorously stirring water (600 ml) containing sodium hydrogencarbonate (1 10 g). The dark brown mixture was extracted with DCM (3 x 200 ml) and the organic phase was washed with water (200 ml) and brine (100ml), dried (MgS04) and concentrated under reduced pressure to afford the title product as a brown oil. H-NMR: [400MHz, CDCI3, ? 8.87 (1 H, d, J = 1.4Hz, ArH), 8.39 (1 H, d, J = 1.9Hz, ArH). | |
With phosphorus(V) oxybromide; In acetonitrile; at 20.0℃;Reflux; | 3-Nitro-5-(trifluoromethyl)pyridin-2-ol (31 .00 g, 149 mmol) was dissolved in acetonitrile (250 ml) to give a dark brown solution. Phosphorus(V) oxybromide (85 g, 298 mmol) was added and the mixture was heated at reflux for 4 hours and then stirred at RT overnight. The reaction mixture was quenched by pouring into vigorously stirring water (600 ml) containing sodium hydrogencarbonate (1 10g). The dark brown mixture was extracted with DCM (3 x 200 ml) and the organic phase was washed with water (200 ml) and brine (100 ml), dried ( MgS04) and concentrated in vacuo to afford the title product as a brown oil. 1H-NMR: [400MHz, CDCI3, deltaEta 8.87 (1 H, d, J = 1.4Hz, ArH), 8.39 (1 H, d, J = 1.9Hz, ArH). | |
2.44g | With phosphorus(V) oxybromide; In acetonitrile; for 16.0h;Reflux; | The 3-nitro-5-trifluoro-Methylpyridin-2-ol (q) (3.12g, 15mmol) in acetonitrile (25 ml) was added to solution POBr 3 (8.6g, 30mmol). Refluxed for 4 hours after stirring at room temperature for 12 hours. The reaction solution is poured into the rapidly stirred sodium bicarbonate (11g) aqueous solution (60 ml). Extraction with methylene chloride mixture (3x20ml), organic phase water (20 ml) and saturated sodium chloride solution (10 ml) after washing, drying by anhydrous sodium sulfate, concentrated to obtain the product (r) (2.44g, 9 . 0mmol) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrabutylammomium bromide; In toluene; for 10.0h;Reflux; | Intermediate A2: 3-Nitro-5-trifluoromethyl-pyridine-2-carbonitrile<strong>[1214336-90-9]2-Bromo-3-nitro-5-trifluoromethyl-pyridine</strong> (10.00 g, 36.87 mmol) was dissolved in toluene (250 ml) with stirring to give a pale yellow solution. Tetrabutylammonium bromide (11.90 g, 36.9 mmol) was added followed by copper(I) cyanide (9.92 g, 111 mmol) and the mixture was heated at reflux for 10 h. After cooling to RT, the reaction mixture was partitioned between water (750 ml) and EtOAc (750 ml). The organic fractions were combined, washed with water (2×250 ml) and brine (100 ml), dried (MgSO4) and concentrated in vacuo to afford the title product. 1H-NMR: [400 MHz, DMSO-d6 deltaH 9.55 (1H, m, ArH), 9.24 (1H, m, ArH) | |
With tetrabutylammomium bromide; In toluene; for 9.0h;Reflux; | 2- Bromo-3-nitro-5-trifluoromethyl-pyridine (10.00 g, 36.87 mmol) was dissolved in toluene (250 ml) with stirring to give a pale yellow solution. Tetrabutylammonium bromide (11.90 g, 36.9 mmol) was added followed by copper(l) cyanide (9.92 g, 1 1 1 mmol) and the mixture was heated at reflux for 9 h. After cooling to RT, the reaction mixture was partitioned between water (750 ml) and EtOAc (750 ml). The organic fractions were combined, washed with water (2 x 250 ml), brine (100 ml), dried (MgS04) and concentrated under reduced pressure to afford the title product. H-NMR: [400MHz, DMSO-d6] ? 9.55 (1 H, m, ArH), 9.24 (1 H, m, ArH) | |
With tetrabutylammomium bromide; In toluene; for 9.0h;Reflux; | <strong>[1214336-90-9]2-Bromo-3-nitro-5-trifluoromethyl-pyridine</strong> (10.00 g, 36.87 mmol) was dissolved in toluene (250 ml) with stirring to give a pale yellow solution. Tetrabutylammonium bromide (11.90 g, 36.9 mmol) was added followed by copper(l) cyanide (9.92 g, 1 1 1 mmol) and the mixture was heated at reflux for 9 h. After cooling to RT, the reaction mixture was partitioned between water (750 ml) and EtOAc (750 ml). The organic fractions were combined, washed with water (2 x 250 ml), brine (100 ml), dried (MgS04) and concentrated under reduced pressure to afford the title product. H-NMR: [400MHz, DMSO-d6] ? 9.55 (1 H, m, ArH), 9.24 (1 H, m, ArH) |
With tetrabutylammomium bromide; In toluene; for 9.0h;Reflux; | 2- Bromo-3-nitro-5-trifluoromethyl-pyridine (10.00 g, 36.87 mmol) was dissolved in toluene (250 ml) with stirring to give a pale yellow solution. Tetrabutylammonium bromide (11.90 g, 36.9 mmol) was added followed by copper(l) cyanide (9.92 g, 1 1 1 mmol) and the mixture was heated at reflux for 9 h. After cooling to RT, the reaction mixture was partitioned between water (750 ml) and EtOAc (750 ml). The organic fractions were combined, washed with water (2 x 250 ml), brine (100 ml), dried (MgS04) and concentrated under reduced pressure to afford the title product. H-NMR: [400MHz, DMSO-d6] ? 9.55 (1 H, m, ArH), 9.24 (1 H, m, ArH) | |
With tetrabutylammomium bromide; In toluene; for 9.0h;Reflux; | <strong>[1214336-90-9]2-Bromo-3-nitro-5-trifluoromethyl-pyridine</strong> (10.00 g, 36.87 mmol) was dissolved in toluene (250 ml) with stirring to give a pale yellow solution. Tetrabutylammonium bromide (1 1 .90 g, 36.9 mmol) was added followed by copper(l) cyanide (9.92 g, 1 1 1 mmol) and the mixture was heated at reflux for 9 hrs. After cooling to RT, the reaction mixture was partitioned between water (750 ml) and EtOAc (750 ml). The organic fractions were combined, washed with water (2 x 250ml) and brine (100ml), dried dried (MgS04) and concentrated in vacuo to afford the title product.1 H-N MR: [400MHz, DMSO-de deltaEta 9.55 (1 H, m, ArH), 9.24 (1 H, m, ArH) | |
1.04g | With tetrabutylammomium bromide; In toluene; for 9.0h;Reflux; | In the 2-bromo-3-nitro-5-trifluoromethyl pyridine (r) (2.0g, 7 . 37mmol) in toluene (50 ml) solution of tetrabutyl ammonium bromide was added (2.2g, 7 . 37mmol) and also cuprous cyanide (CuCN) (1.98g, 22 . 2mmol), refluxed the reaction for 9 hours. after cooling to room temperature, adding water (150 ml) and ethyl acetate (150 ml) mixed. Organic phase water (2x50ml) and saturated sodium chloride solution (20 ml) after washing, drying by anhydrous sodium sulfate, concentrated to obtain the product (s) (1.04g, 4 . 79mmol). |
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