Structure of 762262-09-9
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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. : | 762262-09-9 |
Formula : | C6H8BNO3 |
M.W : | 152.94 |
SMILES Code : | COC1=NC=CC(B(O)O)=C1 |
MDL No. : | MFCD07368877 |
InChI Key : | DHQMUJSACXTPEA-UHFFFAOYSA-N |
Pubchem ID : | 23546919 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 40.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
62.58 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 |
0.06 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.23 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.22 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.1 |
Solubility | 12.2 mg/ml ; 0.0799 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.93 |
Solubility | 18.1 mg/ml ; 0.118 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.03 |
Solubility | 14.4 mg/ml ; 0.094 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 |
-7.19 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 |
1.0 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) |
1.99 |
* 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 |
---|---|---|
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 100.0℃; for 2.0h;Microwave radiation; | To a solution of <strong>[886371-28-4]3-bromo-6-chloro-imidazo[1,2-a]pyridine</strong> (1 eq, 0.72 mmol, 0.2 g), 2- methoxypyrid-4-yl boronic acid (1.0 eq, 0.72 mmol, 0.11 g), Na2COs (2 eq, 1.44 mmol, 0.152 g) in dioxane (0.6 ml) and water (0.2 ml), under an inert atmosphere of argon is added bis(triphenylphosphine)palladium II chloride (50 mg). The reaction mixture is heated using microwave radiation at 100 C for 2 hours. The mixture is diluted with H2O (50 ml) and extracted with EtOAc. The combined organic portions are washed with brine, dried (MgStheta4) and concentrated in vacuo. The residue is <n="120"/>purified by flash chromatography on silica eluting with 0-25% EtOAc in iso-hexane to afford the title compound; [M+H]+ =260 (262). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 90.0℃; for 4.0h;Inert atmosphere; | A solution of (2-methoxypyridin-4-yl)boronic acid (75 mg, 0.490 mmol), 4- bromo-2-(difluoromethyl)-l-fluorobenzene (121 mg, 0.539 mmol), potassium phosphate tribasic (312 mg, 1.471 mmol) and PdCl2(dppf)-CH2Cl2 adduct (20.02 mg, 0.025 mmol) in 1,4-dioxane (3 mL) and water (0.5 mL) was purged with nitrogen and heated to 90 C for 4 h. The reaction mixture was diluted with ethyl acetate (10 mL). The black suspension was filtered through diatomaceous earth (Celite) and the bed was washed with ethyl acetate (10 mL). The residue was purified via silica gel chromatography (15% pet ether: ethyl acetate) to afford 4-(3-(difluoromethyl)-4- fluorophenyl)-2-methoxypyridine (100 mg, 0.363 mmol, 74% yield) as a brown solid. LCMS (ESI) m/e 254.0 [(M+H)+, calcd for C13H11F3NO 254.1]; LC/MS retention time (Method C): tR = 1.02 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium phosphate; chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); In 1,4-dioxane; water; at 100℃; for 5h;Inert atmosphere; | A mixture of 2-chloro-6-(trifluoromethyl)benzoicacid (1 g, 4.45 mmol), X-phos Pd G?. (350 mg, 0.45 mmol), 2-methoxypyridine-4-boronicacid (817 mg, 5.34 mmol) and K3PO4 (3.78 g, 17.81 mmol) in 1,4-dioxane (20 mL) and water (2 mL) were stirred at 100 C for 5 hours under an atmosphere of M2.After cooling to 25 C, the reaction mixture was diluted in water (40 mL). The aqueous layer was extracted with EtOAc (40 mL x 2). Tire combined organic layers were dried over anhydrous NaaSfL, filtered and concentrated under reduced pressure. The crude residue was purified by reverse phase chromatography (acetonitrile 27-57/0.225% FA in water) to give 2-(2-methoxypyridin-4-yl)-6- (trifluoromethyl)benzoic acid (900 mg, yield: 68%) as a white solid. TlNMR (400 MHz, CDCft): d = 8.20 (d, J = 5.6 Hz, 1H), 7.80 (d, J = 8.0 Hz, I I I). 7.67-7.63 (m, H I). 7.57 (d, J = 7.6 Hz, 111). 7.03-7.01 (m, IH), 6.86 (s, 1H), 3.95 (s, 3H), 3.42 (br, s, 1H). |
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