Structure of 450-88-4
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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. : | 450-88-4 |
Formula : | C7H6BrFO |
M.W : | 205.02 |
SMILES Code : | COC1=CC(F)=CC=C1Br |
MDL No. : | MFCD04973752 |
InChI Key : | KGYXKRGMSUHYCY-UHFFFAOYSA-N |
Pubchem ID : | 7018043 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H227-H302+H332-H319-H412 |
Precautionary Statements: | P210-P261-P273-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 40.59 |
TPSA ? Topological Polar Surface Area: Calculated from |
9.23 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 |
2.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.99 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.92 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.79 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.18 |
Solubility | 0.136 mg/ml ; 0.000664 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.53 |
Solubility | 0.611 mg/ml ; 0.00298 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.66 |
Solubility | 0.0446 mg/ml ; 0.000218 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 |
-5.65 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 |
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) |
1.43 |
* 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 sulfuric acid; nitric acid; at 0℃; for 0.5h; | A mixture of 1 -bromo-4-fluoro-2-methoxybenzene (CAS No. [450-88-4]; 10.0 g, 48.8 mmol) in concentrated sulfuric acid (50 mL) was cooled to 0 C and treated dropwise with a freshly prepared mixture of fuming nitric acid (1.05 eq., 2.1 mL, 51 mmol) and concentrated sulfuric acid (1.85 eq., 4.8 mL, 90 mmol). The reaction mixture was stirred at 0 C for 30 minutes and poured in small portions on ice water. The formed precipitate was filtered off, washed with cold water and kept. The filtrate was extracted with ethyl acetate and the organic layer combined with the isolated precipitation. The organic layer was dried with sodium sulfate and concentrated in vacuo. The obtained material was purified by flash chromatography (SiO2-hexane/ ethyl acetate) to give the title compound (5.88 g, 44%). (0555) 1H-NMR (400MHz, DMSO-d6): [ppm] = 4.00 (s, 3H), 7.44 (d, 1 H), 8.40 (d, 1 H).UPLC- MS (ESI-): [M - H]- = 248/250; Rt = 1.17 min (Br isotope pattern; Method E). |
44% | With sulfuric acid; nitric acid; at 0℃; for 0.5h; | A mixture of 1 -bromo-4-fluoro-2-methoxybenzene (CAS No. [450-88-4]; 10.0 g, 48.8 mmol) in concentrated sulfuric acid (50 ml.) was cooled to 0 C and treated dropwise with a freshly prepared mixture of fuming nitric acid (1.05 eq., 2.1 ml_, 51 mmol) and concentrated sulfuric acid (1.85 eq., 4.8 ml_, 90 mmol). The reaction mixture was stirred at 0 C for 30 minutes and poured in small portions on ice water. The formed precipitate was filtered off, washed with cold water and kept. The filtrate was extracted with ethyl acetate and the organic layer combined with the isolated precipitation. The organic layer was dried with sodium sulfate and concentrated in vacuo. The obtained material was purified by flash chromatography (Si02-hexane/ ethyl acetate) to give the title compound (5.88 g, 44%). 1H-NM (400MHz, DMSO-de): delta [ppm] = 4.00 (s, 3H), 7.44 (d, 1 H), 8.40 (d, 1 H).UPLC- UPLC-MS (ESI-): [M - H]" = 248/250; Rt = 1.17 min (Br isotope pattern; Method E). |
44% | With sulfuric acid; nitric acid; at 0℃; for 0.5h; | A mixture of 1 -bromo-4-fluoro-2-methoxybenzene (CAS No. [450-88-4]; 10.0 g, 48.8 mmol) in concentrated sulfuric acid (50 mL) was cooled to 0 C and treated dropwise with a freshly prepared mixture of fuming nitric acid (1.05 eq., 2.1 mL, 51 mmol) and concentrated sulfuric acid (1.85 eq., 4.8 mL, 90 mmol). The reaction mixture was stirred at 0 C for 30 minutes and poured in small portions on ice water. The formed precipitate was filtered off, washed with cold water and kept. The filtrate was extracted with ethyl acetate and the organic layer combined with the isolated precipitate. The organic layer was dried with sodium sulfate and concentrated in vacuo. The obtained material was purified by flash chromatography (Si02-hexane/ ethyl acetate) to give the title compound (5.88 g, 44%).1H-NMR (400MHz, DMSO-de): delta [ppm] = 4.00 (s, 3H), 7.44 (d, 1 H), 8.40 (d, 1 H).UPLC- MS (ESI-): [M - H] = 248/250; R, = 1.17 min (Br isotope pattern; Method E). |
13.2 g | With sulfuric acid; potassium nitrate; at 20℃; for 1.0h;Cooling with ice; | Compound 9 (15 g, 0.073 mol) was dissolved in concentrated sulfuric acid (150 mL), and potassium nitrate (7.4 g, 0.073 mol) was slowly added under cooling in an ice-salt bath. After the completion of addition, the temperature was increased to room temperature to react for 1 h. The reaction solution was poured slowly into ice water, stirred to precipitate solids, and filtered. The filter cake was washed twice with water, and oven-dried to obtain 13.2 g of grey solid. MS (ESI) (m/z): [M+H]+ 250.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃; for 16h;Inert atmosphere; | 1-Bromo-4-fluoro-3-methoxybenzene (773 mg, 3.77 mmol) and bis(pinacolato)diboron (1.24 mg, 4.90 mmol) were dissolved in dioxane (10 mL), and anhydrous potassium acetate (1.11 mg, 11.31 mmol) and [1,1'-bis (diphenylphosphino)ferrocene]dichloropalladium.dichloromethane (276 mg, 0.377 mmol) were added. Under nitrogen gas atmosphere, the mixture was heated to 80 C. and stirred for 16 hours. After cooling to room temperature, the mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel TLC preparative plate (petroleum ether: ethyl acetate=1:1) to give compound 27-a (600 mg, yield 63%). 1H-NMR (400 MHz, CDCl3) δ: 7.65 (t, J=8.0 Hz, 1H), 6.55-6.66 (m, 2H), 3.82 (s, 3H), 1.34 (s, 12H) ppm |
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