Structure of 6942-39-8
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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. : | 6942-39-8 |
Formula : | C8H6BrFO2 |
M.W : | 233.03 |
SMILES Code : | COC(=O)C1=C(Br)C=CC(F)=C1 |
MDL No. : | MFCD00086167 |
InChI Key : | FCMQMRAFVRTHCR-UHFFFAOYSA-N |
Pubchem ID : | 138875 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.38 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.32 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.59 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.8 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.09 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.79 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.92 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.78 |
Solubility | 0.0383 mg/ml ; 0.000164 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.83 |
Solubility | 0.0346 mg/ml ; 0.000148 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.61 |
Solubility | 0.0569 mg/ml ; 0.000244 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 |
-5.17 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 |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.6 |
* 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 |
---|---|---|
44% | With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 2h;Inert atmosphere; Reflux; Sealed vessel; | Methyl 2-bromo-5-fluorobenzoate (1 .0 gram, 4.2 mmol) and (1 H- pyrazol-5-yl)boronic acid (485 mg, 4.6 mmol) were combined and dissolved in degassed DME (15 ml) then treated with NaHCO3 (706 mg, 8.4 mmol) in water and the reaction purged with bubbling N2 for 5 minutes. The reaction was treated with Pd(PPh3) (243 mg (0.2 mmol) and then purged with bubbling for 5 minutes in a sealed vessel and then heated to reflux for 2 h. The reaction mixture was cooled to 23 °C, filtered, and solid rinsed with EtOAc. The organic layers were separated, dried and concentrated. Purification via FCC (ethyl acatate/hexanes, 0-30percent) afforded methyl 5-fluoro-2-(1 H-pyrazol-5-yl)benzoate (415 mg, 44percent). |
44% | With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 2.16667h;Inert atmosphere; Reflux; | Methyl 2-bromo-5-fluorobenzoate (1 .0 g, 4.2 mmol) and (1 H- pyrazol-5-yl)boronic acid (485 mg, 4.6 mmol) were combined and dissolved in degassed DME (15 ml) then treated with NaHCO3 (706 mg, 8.4 mmol) in water and the reaction purged with bubbling N2 for 5 minutes. The reaction was treated with Pd(PPh3)4 (243 mg (0.2 mmol) and then purged with bubbling for 5 minutes in a sealed vessel and then heated to reflux for 2 h. The reaction mixture was cooled to 23 oC, filtered, and solid rinsed with EtOAc. The organic layers were separated, dried and concentrated. Purification via FCC (ethyl acatate/hexanes, 0-30percent) afforded methyl 5-fluoro-2-(1 H-pyrazol-5-yl)benzoate (415 mg, 44percent). |
44% | With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In water; for 2h;Inert atmosphere; Reflux; | Step A: Methyl 2-bromo-5-fluorobenzoate (1 .0 g, 4.2 mmol) and (1 H- pyrazol-5-yl)boronic acid (485 mg, 4.6 mmol) were combined and dissolved in degassed DME (15 ml) then treated with NaHCO3 (706 mg, 8.4 mmol) in water and the reaction purged with bubbling N2 for 5 minutes. The reaction was treated with Pd(PPh3) (243 mg (0.2 mmol) and then purged with bubbling for 5 minutes in a sealed vessel and then heated to reflux for 2 h. The reaction mixture was cooled to 23 C, filtered, and solid rinsed with EtOAc. The organic layers were separated, dried and concentrated. Purification via FCC (ethyl acatate/hexanes, 0-30percent) afforded methyl 5-fluoro-2-(1 H-pyrazol-5-yl)benzoate (415 mg, 44percent). |
With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 2h;Inert atmosphere; Reflux; | Intermediate 51 : 5-Fluoro-2-(1 H-pyrazol-5-yl)benzoic acid. Step A: Methyl 2-bromo-5-fluorobenzoate (1 .0 g, 4.2 mmol) and (1 H- pyrazol-5-yl)boronic acid (485 mg, 4.6 mmol) were combined and dissolved in degassed DME (15 ml) then treated with NaHC03 (706 mg, 8.4 mmol) in water and the reaction purged with bubbling N2 for 5 minutes. The reaction was treated with Pd(PPh3)4 (243 mg (0.2 mmol) and then purged with bubbling for 5 minutes in a sealed vessel and then heated to reflux for 2 h. The reaction mixture was cooled to 23 °C, filtered, and solid rinsed with EtOAc. The organic layers were separated, dried and concentrated. Purification via FCC (ethyl acatate/hexanes, 0-30percent) afforded methyl 5-fluoro-2-(1 H-pyrazol-5-yl)benzoate (415 mg, 44percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With tetrakis(triphenylphosphine) palladium(0); In toluene; at 150℃; for 0.5h;Microwave irradiation; | j0363] To a solution of methyl 2-bromo-5-fluorobenzoate (1.1 g, 4.8 mmol) and <strong>[145214-05-7]2-(tri-n-butylstannyl)oxazole</strong> (1.3 mE, 6.2 mmol) in toluene (14 mE) was added Pd(PPh3)4 (550 g,0.476 mmol), and the reaction mixture was heated via microwave heating to 150 C. for 30 mm. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were dried over Mg504, filtered and concentrated. Purification via silica gel chromatography (0-40% EtOAc in hexanes, followed by a second column 0-10% EtOAc in hexanes) gave the title compound (553 g, 5 2%). MS (ESI) mass calcd. for C11H6FN03, 221.1; mlz found 222.1 [M+H]. |
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