Structure of 79456-26-1
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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. : | 79456-26-1 |
Formula : | C6H4ClF3N2 |
M.W : | 196.56 |
SMILES Code : | NC1=NC=C(C=C1Cl)C(F)(F)F |
MDL No. : | MFCD00042154 |
InChI Key : | WXNPZQIRDCDLJD-UHFFFAOYSA-N |
Pubchem ID : | 607248 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H412 |
Precautionary Statements: | P273 |
Num. heavy atoms | 12 |
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 | 38.65 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.91 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.53 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.02 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.5 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.92 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.33 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.64 |
Solubility | 0.455 mg/ml ; 0.00232 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.46 |
Solubility | 0.675 mg/ml ; 0.00343 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.17 |
Solubility | 0.132 mg/ml ; 0.000673 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) |
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 |
-6.06 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 |
0.0 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) |
1.87 |
* 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 |
---|---|---|
93% | In ethanol; at 20 - 80℃; for 12.0h; | Intermediate 10; 8-Chloro-6-(trifluoromethyl)imidazo[l,2-fl]pyridine-2-carboxylic acid; Ethyl 8-chloro-6-(trifluoromethyl)-imidazo [ 1 ,2-a] pyridine-2-carboxylate (9).; To a stirred solution of 2-amino-3-chloro-5-trifluoromethyl pyridine 7 (12.5 g, 63.6 mmol) in EtOH (125 rnL) was added ethyl bromopyruvate 8 (20 mL, 159 mmol) at room temperature. The resulting mixture was heated to 80 0C for 12 h. The reaction mixture was cooled to ambient temperature and concentrated. The residue was suspended in diethyl ether and the resulting solid was filtered and dried under vacuum to afford 9 (17.3g, 93% yield) as a light yellow solid. |
86% | In ethanol; at 80℃; for 48.0h; | To a stirred solution of 2-amino-3-chloro-5-trifluoromethylpyridine (5) (50.0 g, 0.25 mmol) in EtOH (500 mL) was added ethylbromopyruvate (80.0 mL,0.64 mol) at room temperature. The reaction mixture was heated at 80C for 48 h and then cooled to room temperature. The mixture was concentrated and the residue was suspended in diethyl ether. The resulting precipitate was collected by filtration and dried under vacuum to afford ethyl 8-chloro- 6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylate (6) (64.0 g, 86%) as an off-white solid. |
86% | In ethanol; at 80℃; for 48.0h; | [00253] To a stirred solution of 2-amino-3-chloro-5-trifluoromethylpyridine (5) (50.0 g, 0.25 mmol) in EtOH (500 mL) was added ethylbromopyruvate (80.0 mL,0.64 mol) at room temperature. The reaction mixture was heated at 80C for 48 h and then cooled to room temperature. The mixture was concentrated and the residue was suspended in diethyl ether. The resulting precipitate was collected by filtration and dried under vacuum to afford ethyl 8-chloro- 6-(trifluoromethyl)imidazo[l,2- ]pyridine-2-carboxylate (6) (64.0 g, 86%) as an off-white solid. |
86% | In ethanol; at 80℃; for 48.0h; | To a stirred solution of 2-amino-3-chloro-5-trifluoromethylpyridine (30) (50.0 g, 0.25 mmol) in EtOH (500 mL) was added ethylbromopyruvate (80.0 mL, 0.64 mol) at room temperature. The reaction mixture was heated at 80C for 48 h and then cooled to room temperature. The mixture was concentrated and the residue was suspended in diethyl ether. The resulting precipitate was collected by filtration and dried under vacuum to afford ethyl 8-chloro- 6-(trifluoromethyl)imidazo[ 1 ,2-a]pyridine-2-carboxylate (31) (64.0 g, 86%) as an off-white solid. |
75% | In tetrahydrofuran;Reflux; | 2-amino-3-chloro-5-trifluoromethylpyridine 3.92 g (20 mmol) was added to a 250 ml bottle.Ethyl 3-bromopyruvate3.9 g (20 mmol), 100 ml of tetrahydrofuran, and heated to reflux.TLC followed the progress of the reaction, and after the reaction was completed, the solvent was distilled off under reduced pressure.A saturated sodium chloride solution (60 mL) was added to the residue and dichloromethane (50 mL×3)The organic phases were combined, dried over anhydrous sodium sulfate, concentrated and dried.The white solid product was obtained 4.4 g, yield 75%. |
In 1,2-dimethoxyethane; at 0 - 25℃; for 72.0h; | To a solution of 2-amino-3-chloro-5-(trifluoromethyl)pyridine (24.7 g, 126 mmol) in 1 ,2-dimethoxyethane (260 mL) at 0 0C was added ethyl bromopyruvate (17.43 mL, 138 mmol) dropwise. The reaction mixture was warmed to room temperature and stirred for three days to form a suspension. The reaction mixture was then extracted with dichloromethane (2 x 200 mL) and washed with water (2 x 200 mL). The combined dichloromethane extracts were dried over magnesium sulfate and concentrated under reduced pressure to obtain a solid residue. The combined water washes were saturated with sodium carbonate, extracted with ethyl acetate (2 x 200 mL), and dried over magnesium sulfate. The combined ethyl acetate extracts and the residue obtained from the concentration of the dichloromethane were combined, and the mixture was concentrated under reduced pressure to obtain a solid.This solid was dissolved in ethanol (800 mL), and aqueous 50 % sodium hydroxide(40 g, 500 mmol) combined with additional water (150 mL) was added dropwise. The reaction mixture was stirred at room temperature overnight to form a suspension. The reaction mixture was acidified to pH 2 with concentrated hydrochloric acid and then cooled and stirred for several hours to precipitate a solid. The solid product was isolated by filtration using a glass-fritted filter funnel, washed with water, and air dried under a stream of air overnight to afford 13 g of the title compound as a solid. 1H NMR (CDCl3) δ 8.51 (s, IH), 8.40 (s, IH), 7.55 (s, IH). |
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