Structure of 1072951-54-2
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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. : | 1072951-54-2 |
Formula : | C5H4BCl2NO2 |
M.W : | 191.81 |
SMILES Code : | OB(O)C1=CC(Cl)=NC(Cl)=C1 |
MDL No. : | MFCD09751352 |
InChI Key : | JFUQZFQJFYZZGY-UHFFFAOYSA-N |
Pubchem ID : | 46739131 |
GHS Pictogram: |
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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 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 44.08 |
TPSA ? Topological Polar Surface Area: Calculated from |
53.35 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.07 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.36 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.43 |
Solubility | 0.72 mg/ml ; 0.00376 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.41 |
Solubility | 0.738 mg/ml ; 0.00385 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.15 |
Solubility | 1.35 mg/ml ; 0.00706 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 |
-6.28 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) |
1.87 |
* 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 |
---|---|---|
n-BuLi (3 mL, 2.5 M in hexane, 1.50 equiv) was added dropwise into a solution of 2,6- dichloro-4-iodopyridine (1.40 g, 5.112 mmol, 1.00 equiv) in tetrahydrofuran (20 mL) at -78C under nitrogen. The resulting solution was stirred for 30 mm at -78C. Trimethyl borate (580 mg, 5.582 mmol, 1.10 equiv) was added at -78C and the reaction was stirred for 1 h at -78C. The resulting solution was stirred for an additional 12 h at room temperature, quenched by 1.6 g of pinacol and then AcOH (0.6 mL). The solids were filtered out and the liquid was concentrated under vacuum. This resulted in the title compound (1 g, crude) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With Pd(2-[2-(benzylthio)phenyliminomethyl]-4-bromophenol-(H))Cl; potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 5h;Sealed tube; Inert atmosphere; | General procedure: A sealed tube was charged with sulfenyl chloride 2a (219mg, 1 mmol), phenylboronic acid (3a) (135 mg, 1 mmol),K2CO3 (254 mg, 2 mmol), catalyst 1a (2 mol%, 10 mg) andDMF (2 mL). The mixture was stirred at 90 C under an N2atm for 5 h. After completion of the reaction, the mixturewas cooled to r.t. and extracted with EtOAc (2 × 10 mL). The combined extracts were dried over anhydrous Na2SO4,filtered and the solvent removed under reduced pressure.The crude residue was purified by flash chromatographyover silica gel to provide product 4a (166 mg, 89%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 2h;Inert atmosphere; | Example 29.N-(3-chloro-6?-(S-( i-methyl-i H-pyrazol-4-yl)- 1 H-benzo[d}imidazol- l-yl)-[2,4?- bipyridinj-2?-yl)cyclopropanesulfonamidea) 2?,3,6?-Trichloro-2,4?-bipyridine A solution of <strong>[1072951-54-2](2,6-dichloropyridin-4-yl)boronic acid</strong> (0.76 g, 4 mmol) in 1,2- dimethoxyethane (15 ml) was degassed by N2 bubbling for 5 mm. 2-Bromo-3-chloro- pyridine (0.7 g, 3.63 mmol, 1.2 eq) was added and the mixture was degassed for another 5 mm. Pd(dppf)C12 (0.3 g, 0.36 mmol, 0.1 eq) and aqueous sodium carbonate (1.15 g,10.9 mmol, 3 eq) were added sequentially using the procedure of Intermediate Example1 and then heated at 90 C for 2 h. The reaction mixture was then quenched and extracted as in Intermediate Example 1. The solvent was distilled off to afford the crude residue which was purified by column chromatography (60-120 silica gel, 10 % ethyl acetate in hexane) to afford the title product in 74 % yield (0.7 g). ?H NMR (300 MHz,CDC13): oe 8.63 (dd, 1H),7.86 (m, III), 7.68 (s, 2H), 7.37 (dd, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 120℃; for 12h;Inert atmosphere; | A mixture of 2-bromo-5-(trifluoromethyl)pyridine (800.00 mg, 3.54 mmol, 1.00 equiv), (2,6- dichloropyridin-4-yl)boronic acid (1 g, 5.21 mmol, 1.00 equiv), Pd(dppf)C12.CH2C12 (290 mg, 0.36 mmol, 0.10 equiv), and potassium carbonate (1.96 g, 14.18 mmol, 4.00 equiv) in 1,4-dioxane (40 mL) /water(2 mL) was stuffed for 12 h at 120C under nitrogen. The resulting solution was diluted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/petroleum ether (1:100). This resulted in the title compound (680 mg, 66%) as a white solid. |
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