Structure of 885588-12-5
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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. : | 885588-12-5 |
Formula : | C6H3BrFNO2 |
M.W : | 220.00 |
SMILES Code : | OC(=O)C1=CC(Br)=NC=C1F |
MDL No. : | MFCD09261246 |
InChI Key : | VRHKBNFQGHNLIJ-UHFFFAOYSA-N |
Pubchem ID : | 46739277 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-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 | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.85 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.17 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.1 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.09 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.49 |
Solubility | 0.717 mg/ml ; 0.00326 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.16 |
Solubility | 1.52 mg/ml ; 0.00689 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.54 |
Solubility | 0.639 mg/ml ; 0.0029 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 |
-6.58 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 |
0.56 |
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) |
1.85 |
* 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 |
---|---|---|
81% | With thionyl chloride; | Methyl 2-bromo-5-fluoroisonicotinate:; To a solution of 2-bromo-5-fluoroisonicotinic acid (1.5 g, 6.82 mmol) in methanol (75 ml), thionyl dichloride (2.5 ml, 34.09 mmol) was added drop-wise. The reaction mixture was stirred overnight. The solvent was removed under high vacuum. The residual solid was distilled at 90 0C under vacuum to get 1.3g (81 %) of pure methyl 2-bromo-5- fluoroisonicotinate: |
73% | With thionyl chloride; at 0 - 20℃; for 16.0h; | To a stirred solution of 2-bromo-5-fluoroisonicotinic acid (2.8 g, 12.78 mmol) in MeOH (30 ml), SOCI2 (7.54 g,63.9 mmol) was added at ooc and it was allowed to stir at rt for 16h. The reaction mixture was concentratedunder reduced pressure and the residue was dissolved in water (100 ml), basified to pH-8 using saturated NaHC03 solution, and extracted with EtOAc (2 x 100 ml). The combined organic layers were dried overanhydrous Na2S04, filtered and concentrated under reduced pressure to afford the title compound (2.2 g, 73%)as a pale yellow solid;LC-MS (method 8): Rt = 2.41 min; m/z = 234.07 (M+H+). |
10.3 g | With thionyl chloride; In methanol; at 0 - 20℃; for 24.5h; | To a solution of 2-bromo-5-fluoro-pyridine-4-carboxylic acid (10.0 g, 45.5 mmol) in methanol (300 mL) cooled to 0C was added thionyl chloride (16.5 mL, 227.3 mmol) dropwise over 30 minutes. The reaction mixture was stirred at ambient temperature for 24 hours. Toluene (40 mL) was added to the reaction mixture. After evaporation of methanol, thionyl chloride was distilled out. The remaining toluene was evaporated on rotary evaporator affording the cmde product, which was dissolved in dichloromethane (30 mL) evaporated under reduced pressure affording methyl 2-bromo-5 -fluoropyridine-4-carboxylate (10.3 g). LCMS: MW (calcd): 232.9; MS (ES, m/z): 234, 236 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.4% | In methanol; benzene; for 1.5h;Cooling; | a) methyl 2-bromo-5-fluoroisonicotinate To a cooled solution of 2-bromo-5-fluoroisonicotinic acid (3.0 g, 13.6 mmol) in benzene (20 ml) and methanol (10 ml) is dropwise over a period of 15 min added under stirring and cooling (trimethylsiliyl)diazomethane (2 M in ether, 14 ml, 28 mmol). The yellow solution is stirred for 1.5 h without cooling and evaporated to dryness. Purification of the residue (3.3 g) by chromatography on a 50 g Silicycle silica cartridge using a heptane/ethyl acetate 10-50% gradient affords methyl 2-bromo-5-fluoroisonicotinate (2.82 g, 88.4%) as a light yellow solid. mp.: 43-6 C. MS: m/z=233.9 (M+H+). |
88.4% | In methanol; benzene; for 1.75h;Cooling; | To a cooled solution of 2-bromo-5-fluoroisonicotinic acid (3.0 g, 13.6 mmol) in benzene (20 ml) and methanol (10 ml) is dropwise over a period of 15 min added under stirring and cooling (trimethylsiliyl)diazomethane (2 M in ether, 14 ml, 28 mmol). The yellow solution is stirred for 1.5 h without cooling and evaporated to dryness. Purification of the residue (3.3 g) bychromatography on a 50 g Silicycle silica cartridge using a heptane / ethyl acetate 10-50% gradient affords methyl 2-bromo-5-fluoroisonicotinate (2.82 g, 88.4%) as a light yellow solid, mp.: 43 - 6C. MS: m/z= 233.9 (M+H+). |
10.46 g | In methanol; diethyl ether; toluene; at 0 - 20℃; for 2.5h; | To a solution of 2-bromo-5-fluoro-pyridine-4-carboxylic acid (10.0 g, 45.5 mmol) in methanol (35 mL) and toluene (65 mL) cooled to 0C was added (trimethylsilyl)diazomethane (2.0 M solution in diethyl ether; 45.5 mL, 90.9 mmol) dropwise over 30 minutes. The reaction mixture was stirred at ambient temperature. After 2h, the reaction mixture was evaporated under reduced pressure affording the cmde product, which was dissolved in ethyl acetate (50 mL), washed with water (100 mL) and brine (50 mL) respectively, filtered through phase separator filter and evaporated under reduced pressureaffording methyl 2-bromo-5-fluoro-pyridine-4-carboxylate (10.46g). LCMS: MW (calcd): 232.9; MS (ES, m/z): 234, 236 (M+H). |
In methanol; hexane; toluene; at 20℃; for 1.0h; | 2-Bromo-5-fluoroisonicotinic acid(1.1 g) was mixed in toluene (15 mL) and methanol (5 mL).To this mixture was added 2M trimethylsilyldiazomethane / hexane solution at room temperature.The reaction mixture was stirred at room temperature for 1 hour.By concentrating the reaction mixture under reduced pressure,The title compound (1.17 g) was obtained as a crude product. |
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