Structure of 2252-37-1
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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. : | 2252-37-1 |
Formula : | C7H4BrFO2 |
M.W : | 219.01 |
SMILES Code : | O=C(O)C1=C(F)C=CC=C1Br |
MDL No. : | MFCD01569539 |
Boiling Point : | No data available |
InChI Key : | MDAZJVAIZVUWDE-UHFFFAOYSA-N |
Pubchem ID : | 302621 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-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 | 1.0 |
Molar Refractivity | 41.06 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.38 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.28 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.32 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.09 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.34 |
Solubility | 0.997 mg/ml ; 0.00455 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.66 |
Solubility | 4.76 mg/ml ; 0.0217 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.91 |
Solubility | 0.269 mg/ml ; 0.00123 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 |
-6.73 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 |
0.0 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) |
1.3 |
* 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 |
---|---|---|
85% | With sulfuric acid; at 80℃; for 12h; | Step 1 : Synthesis of methyl 2-bromo-6-fluorobenzoate (2).[00363] 2-Bromo-6-fluorobenzoic acid (1, 12.50 g, 57 mmol) was dissolved in a mixture of methanol (60 mL) and cone, sulfuric acid (65 mL). The solution was heated to 80 C and stirred for 12 h. The reaction mixture was cooled and 20% sodium carbonate solution (500 mL) was added slowly to reach pH = 8. The mixture was extracted with dichloromethane (3 x 180 mL), and the combined organic layers were dried over magnesium sulfate and evaporated. The title compound (11.29 g, 48.5 mmol, 85%) was obtained as a brown oil. |
85% | With sulfuric acid; at 80℃; for 12h; | [00499] 2-Bromo-6-fluorobenzoic acid (37) (12.50 g, 57 mmol) was dissolved in a mixture of methanol (60 mL) and cone, sulfuric acid (65 mL). The solution was heated to 80 C and stirred for 12 h. The reaction mixture was cooled and 20% sodium carbonate solution (500 mL) was added slowly to reach pH = 8. The mixture was extracted with dichloromethane (3 x 180 mL), and the combined organic layers were dried over magnesium sulfate and evaporated. The title compound (11.29 g, 48.5 mmol, 85%) was obtained as a brown oil. |
63% | With sulfuric acid; at 80℃; for 12h; | Asolution containing 2-bromo-6-fluorobenzoic acid (1.0equiv, 0.30 g, 1.37 mmol) and sulfuric acid (1.6 mL) in methanol (1.4 mL) washeated at 80 C for 12 h. The reaction was quenched with satd. aqueous Na2CO3until pH 8, and the aqueous phase was extracted with CH2Cl2(2 x 10 mL). The combined organic extracts were washed with water (20 mL),brine (20 mL), dried over Na2SO4 and filtrated.Evaporation of the solvent under reduced pressure followed by flashchromatography (SiO2, 95/5 hexane/EtOAc) afforded 200 mg (63%) ofthe entitled ester as a yellow oil. 1H-NMR (400 MHz, CDCl3, 25 C): d 7.40 (ddd, J = 8.3, 0.8, 0.8Hz, 1H), 7.27 (ddd, J = 8.3, 8.3, 5.8Hz, 1H), 7.09 (ddd, J = 8.8, 8.3, 0.8 Hz, 1H), 3.98 (s, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In acetonitrile; | 17.1 Ethyl 2-bromo-6-fluorobenzoate To a solution of 2-bromo-6-fluoro-benzoic acid (5 g, 22.83 mmol) and Cs2CO3 (14.9 g, 45.7 mmol) in CH3CN (100 mL) was added CH3CH2I (7.12 g, 45.7 mmol) dropwise. The mixture was stirred at 30 C. overnight. The mixture was filtered and the filtrate was concentrated. The residue was purified by silica gel column chromatography, eluting with PE/EA (10:1) to give the title compound as a colorless oil (2 g, 25%). LCMS (ESI+): m/z 247.249. (M+H)+, Rt: 0.93 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.7% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 4h; | To a solution 2-bromo-6-fluorobenzoic acid (50 g, 0.229 mol) and potassium carbonate (31.6 g, 0.229 mol) in N,N-dimethylformamide (250 mL) was added dropwise methyl iodide (51.83 g, 0.365 mol) over a 30 minute period. The reaction mixture was stirred at RT for 3.5 hours. The resulting mixture was diluted with water (500 mL) and extracted with EtOAc (3*300 mL). The combined organic layers were washed with 1M aqueous HCl (100 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the title compound (53 g, 99.7%). |
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