Structure of 351019-18-6
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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.
Synonyms: 6-Fluoropyridine-3-boronic acid
4.5
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Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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CAS No. : | 351019-18-6 |
Formula : | C5H5BFNO2 |
M.W : | 140.91 |
SMILES Code : | C1=C(C=CC(=N1)F)B(O)O |
Synonyms : |
6-Fluoropyridine-3-boronic acid
|
MDL No. : | MFCD03411559 |
InChI Key : | OJBYZWHAPXIJID-UHFFFAOYSA-N |
Pubchem ID : | 2783397 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-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 | 2.0 |
Molar Refractivity | 34.02 |
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 |
0.19 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.93 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.72 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.43 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.21 |
Solubility | 8.66 mg/ml ; 0.0615 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.87 |
Solubility | 19.1 mg/ml ; 0.135 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.17 |
Solubility | 9.57 mg/ml ; 0.0679 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 |
-7.02 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) |
2.3 |
* 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 |
---|---|---|
94% | With potassium carbonate;[1,3-bis(2,6-diisopropylphenyl)imidazolidene](3-chloropiridyl)palladium(II) dichloride; In 1,4-dioxane; water; at 100℃; | i) 2-(6-Fluoropyridin-3-yl)quinoline-4-carboxylic acid6-Fluoropyridine-3-boronic acid (1.6 g, 12 mmol), a IM aq. solution OfK2CO3 (25 mL) and PEPPSI (0.18 g, 0.26 mmol) were added sequentially to a solution of 2-chloro- quinoline-4-carboxylic acid (2.0 g, 9.6 mmol) in dioxane (25 mL). The reaction mixture was degassed and then heated at 1000C under a nitrogen atmosphere for 2h and then cooled to rt. The dioxane was removed by concentration in vacuo and the remaining residue was diluted with MeOH and citric acid to give a mixture of pH ~ 4. The layers were separated <n="244"/>and the aqueous phase was extracted with EtOAc. The combined organic layers were dried followed by concentration in vacuo to give the title compound (2.8 g, 94percent). 1H NMR (400 MHz, DMSO-J6) delta 9.10 (s, IH), 8.87-8.78 (m, IH), 8.60 (d, IH), 8.49 (s, IH), 8.15 (d, IH), 7.84 (t, IH), 7.74-7.67 (m, IH), 7.39-7.32 (m, IH); m/z (M+H)+ 269.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; for 15h;Inert atmosphere; Reflux; | 13c) Methyl 6-(6-fluoro-3-pyridinyl)-lH-indole-3-carboxylateMethyl 6-bromo-lH-indole-3-carboxylate (0.63 g, 2.48 mmol), 2- fluoropyridyl-5-boronic acid (0.435 g, 3.09 mmol), tetrakistriphenylphosphine palladium (0) (0.14 g, 0.012 mmol), 2 M sodium carbonate (5 mL, 10 mmol), and 1,2- dimethoxyethane (20 mL) were combined and heated at reflux with stirring under a nitrogen atmosphere for 15 hours. The reaction mixture was allowed to cool at room temperature and partitioned between water and ethyl acetate. The organic phase was separated, dried over magnesium sulfate, filtered, and the filtrate was concentrated to give the crude product as a yellow solid. The crude product was purified by flash chromatography over silica gel with a dichloromethane methanol gradient (100:0 to 97:3) to give 0.606 g of methyl 6-(6-fluoro-3-pyridinyl)-lH-indole-3-carboxylate as a yellow solid. 1H NMR indicates that a minor impurity is present. The compound was used without further purification. 1H NMR (J6-DMSO, 400 MHz): delta 12.09 (br s, IH), 8.54 (d, J = 2 Hz, IH), 8.28 (dt, J = 8, 3 Hz, IH), 8.13 (d, J = 3 Hz, IH), 8.06 (d, J = 8 Hz, IH), 7.73 (s, IH), 7.51 (dd, J = 8, 2 Hz, IH), 7.27 (dd, J = 9, 3 Hz, IH), 3.80 (s, 3H). ES-LCMS m/z 269 (M - H)". |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; for 3.0h;Inert atmosphere; Reflux; | Synthesis of 135 To a mixture of 79 (627 mg, 3.0 mmol), 99 (465 mg, 3.3 mmol) and 1,2-dimethoxyethane (20 ml), an aqueous 2M sodium carbonate solution (3 ml, 6.0 mmol) and tetrakistriphenylphosphine palladium (173 mg, 0.15 mmol) were added under an argon atmosphere, and the mixture was heated at reflux for 3 hours. The reaction solution was allowed to return to room temperature, diluted with ethyl acetate and then washed in turn with water and saturated saline. The organic layer was dried and the solvent was distilled off under reduced pressure, and then the residue was purified by silica gel flash column chromatography (eluting solvent: n-hexane/ethyl acetate = 4/1, 3/1) to obtain 135 (700 mg, 87%) as a pale yellow solid. mp 159-161C APCI-MS m/z 270[M+H]+ |
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