Structure of 112204-58-7
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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. : | 112204-58-7 |
Formula : | C6H4BrFO |
M.W : | 191.00 |
SMILES Code : | OC1=CC(Br)=CC=C1F |
MDL No. : | MFCD07782066 |
InChI Key : | YPTHSYKJDRMAJY-UHFFFAOYSA-N |
Pubchem ID : | 183421 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 36.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.85 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.36 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.67 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.48 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.42 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.0 |
Solubility | 0.189 mg/ml ; 0.00099 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.43 |
Solubility | 0.718 mg/ml ; 0.00376 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.96 |
Solubility | 0.211 mg/ml ; 0.00111 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 |
-5.79 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 |
2.0 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.47 |
* 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 |
---|---|---|
86% | With boron tribromide; In dichloromethane; at 20℃; | To a stirred solution OF 4-BROMO-1-FLUORO-2-METHOXYBENZENE (1.00 g, 4.88 mmol) in anhydrous CH2CL2 (20 ml) was added dropwise in an ice bath BBR3 (1 M solution in CH2Cl2, 9.75 ml, 9. 75 mmol), and the mixture was stirred at room temperature overnight. The reaction was cooled in an ice bath and quenched by adding MEOH (1.0 ml) dropwise. The solvent was evaporated and the residue purified by flash chromatography eluting with ISOHEXANE/CH2CL2/MEOH (70: 20: 10) to leave 0.802 g (86%) of the title compound: BH (400 MHz, CDCL3) 5.24 (1 H, s), 6.96 (2 H, m), 7.16 (1 H, DD, J7. 7,2. 0 HZ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 65h; | Reference Example-13 Potassium carbonate (18.8 g, 136 mmol) and methyl iodide (19.3 g, 136 mmol) were added to a solution of 5-bromo-2-fluorophenol (13.0 g, 68.1 mmol) in DMF (120 mL), followed by stirring at room temperature for 65 hours. After the reaction was completed, water (150 mL) was added to the reaction solution, and the resultant product was extracted with ethyl acetate (100 mL*1, 50 mL*2). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, whereby a pale yellow oily crude product (29.0 g) was obtained. This was purified by silica gel column chromatography (hexane:ethyl acetate=10:1), whereby 5-bromo-2-fluoroanisole (14.2 g, yield: quantitative) was obtained as a colorless oily material. 1H-NMR (400 MHz, CDCl3): delta3.88 (s, 3H), 6.95 (dd, J=8.6 and 10.8 Hz, 1H), 7.02 (ddd, J=2.2, 4.2 and 8.6 Hz, 1H), 7.08 (dd, J=2.2 and 7.6 Hz, 1H). 19F-NMR (376 MHz, CDCl3): delta-137 (s, 1F). |
77% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 40℃; for 2h; | 100204] To a solution of 23 A (3.3 g, 17.3 mmol) and K2CO3 (4.78 g, 34.6 mmol) in DMF (20 mL) was added methyl iodide (1.46 niL, 23.4 mmol) at rt. The mixture was heated at 400C for 2.0 h. After cooling to rt, it was diluted with diethyl ether, washed with water and brine, dried over MgS O4. The crude residue was purified by flash column chromatography (EtOAc:hexanes = 1 : 6) to give 2.74 g(77%) of 23B as a viscous oil. 1H NMR (400 MHz, CDCl3) delta ppm 3.89 (s, 3 H), 6.95 - 7.00 (m, 3 H). |
77% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 40℃; | To a solution of 7A (3.3 g, 17.3 mmol) and K2CO3 (4.78 g, 34.6 mmol) in DMF (20 mL) was added methyl iodide (1.46 mL, 23.4 mmol) at rt. The mixture was heated at 40 C. for 2.0 h. After cooling to rt, it was diluted with diethyl ether, washed with water and brine, dried over MgSO4. The crude residue was purified by flash column chromatography (EtOAc:hexanes=1:6) to give 2.74 g (77%) of 7B as a viscous oil. 1H NMR (400 MHz, CDCl3) delta ppm 3.89 (s, 3H), 6.95-7.00 (m, 3H). |
77% | With potassium carbonate; In N,N-dimethyl-formamide; at 40℃; for 2h; | To a solution of 64A (3.3 g, 17.3 mmol) and K2CO3 (4.78 g, 34.6 mmol) in DMF (20 mL) was added methyl iodide (1.46 mL, 23.4 mmol) at rt. The mixture was heated at 40 C. for 2.0 h. After cooled to rt, it-was diluted with ether, washed with water and brine, dried over MgSO4. The crude residue was purified by flash column chromatography (EtOAc:hexanes=1:6) to give 2.74 g (77%) of 69A as viscous oil. 1H NMR (400 MHz, CDCl3) delta ppm 3.89 (s, 3 H), 6.95-7.00 (m, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.3% | With potassium carbonate; In acetone; at 60℃; for 16h; | A solution of <strong>[19047-31-5]2-chloro-N-cyclopropylacetamide</strong> (1.0 g, 7.5 mmol), 5-bromo-2- fluorophenol (1.44 g, 7.5 mmol) and K2C03 (1.55 g, 11.25 mmol) in 30 mL of acetone was heated at 60 C for 16 h. The mixture was filtered and concentrated to give a residue, which was purified by column chromatography (PE/EA, 2/1) to give the title as a yellow solid (1.2 g, 55.3 %). m/e 288 (M+H)+. |
55.3% | With potassium carbonate; In acetone; at 60℃; for 16h; | Example 96 2-(5-Bromo-2-fluorophenoxy)-N-cyclopropylacetamide A solution of <strong>[19047-31-5]2-chloro-N-cyclopropylacetamide</strong> (1.0 g, 7.5 mmol), 5-bromo-2- fluorophenol (1.44 g, 7.5 mmol) and K2C03 (1.55 g, 11.25 mmol) in 30 mL of acetone was heated at 60 C for 16 h. The mixture was filtered and concentrated to give a residue, which was purified by column chromatography (PE/EA, 2/1) to give the title as a yellow solid (1.2 g, 55.3 %). m/e 288 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate; In acetonitrile; at 70℃; for 16h; | [0481] To the mixture of 5-bromo-2-fluoro-phenol (600.00 mg, 3.14 mmol), 2-chloro-N- lsopropylacetamide (510.90 mg, 3.77 mmol) in MeCN (15.00 mL) was added K2C03 (867.96 mg, 6.28 mmol). The mixture was stirred at 70 C for 16 h. LCMS showed one main peak of desired product. The reaction mixture was diluted with water (40 mL) and the mixture was extracted with EtOAc (40 mLx3). The combined organic layers were dried over Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, petroleum ether/EtOAc=l :0 to 4: 1) to give the title compound (900.00 mg, 98%) as light yellow solid. 1H NMR (400 MHz, DMSO-i/6) delta 7.97 (d, J= 7.2 Hz, 1H), 7.25- 7.20 (m, 2H), 7.17-7.16 (m, 1H), 4.58 (s, 2H), 3.95-3.87 (m, 1H), 1.08 (d, J= 6.8 Hz, 6H). |
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