Structure of 17318-08-0
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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. : | 17318-08-0 |
Formula : | C6H2BrCl2F |
M.W : | 243.89 |
SMILES Code : | BrC1=CC(=C(C(=C1)Cl)F)Cl |
MDL No. : | MFCD09996901 |
InChI Key : | MMJSIYGLDQNUTH-UHFFFAOYSA-N |
Pubchem ID : | 22926230 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.38 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.97 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.63 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.24 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.3 |
Solubility | 0.0123 mg/ml ; 0.0000504 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.67 |
Solubility | 0.052 mg/ml ; 0.000213 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.77 |
Solubility | 0.00417 mg/ml ; 0.0000171 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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) |
Yes |
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 |
-4.97 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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 |
2.0 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) |
1.9 |
* 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 |
---|---|---|
3.5 g | Intermediate 3: 1-(4-chloro-3,5-difluorophenyl)-2,2,2-trifluoroethanone 5-Bromo-2-fluoro-1 ,3-dichlorobenzene (7.0 g, 28.7 mmol) was stirred at room temperature in THF (50 ml_) under argon and isopropylmagenesium chloride lithium chloride complex (24.3 ml_, 1.3 M in THF, 1.1 eq) was added over 1 min and stirred at RT for 30 min. To this was added piperidine trifluoroacetamide (5.6 ml_, 1.32 eq) over about 1 minute at 0C and the reaction was stirred at room temperature for 2 h. The reaction was quenched with aqueous saturated NH4CI (50 ml_) and extracted with MTBE (2 x 50 ml_). Solvents were removed under reduced pressure and the crude product was purified using 12 g Redi-Sep column, eluting with 0 to 50% ethyl acetate in heptanes, to yield 3.5 g of 1-(4-chloro-3,5-difluorophenyl)-2,2,2- trifluoroethanone. H-NMR (400 MHz, CDCI3) delta ppm 8.06 (dd, 2H, J1 = 6.2 Hz, J2 = 0.9 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one (Intermediate Compound 9) (0328) (0329) 9 (0330) [0164] To a cooled (10 C) solution of 1-bromo-3,5-dichloro-4-fluorobenzene (1.10 kg, 4.51 mol) in THF (9.70 L) was added /-PrMgCI LiCI (3.64 L, 4.74 mol, 1.3 molar) while maintaining the internal temperature at < 20 C. The reaction was stirred for 2 hours with an internal temperature of 18 C, before cooling to - 9 C. Methyl trifluoroacetate (499 ml_, 4.96 mol) was added while maintaining the internal temperature < 10 C. Reaction was warmed to 20 C and stirred for 3 hours before it was quenched with 4 molar HCI (1.50 L). The biphasic mixture was stirred 2 hours before it was diluted with heptane (4 L). The reaction was mixed for 10 min. and the layers allowed to separate. The aqueous layer was removed extracted 1X 2 L EtOAc and the combined organic fractions were washed 1 X 4L 22% aq. NaCI and dried over MgS04 (1.5 kg) for 15 hours. The organic solution was filtered and concentrated in vacuo. The residue was dissolved in toluene (4 L) and concentrated in vacuo. The resultant oil was dissolved in toluene (4 L) and concentrated in vacuo a second time to give 1.06 kg of 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one (89%) that was 91% pure. (0331) [0165] Note that the yields for smaller scale reactions have ranged between 60 - 94% for this experiment. (0332) [0166] 1H NMR (400MHz, CHLOROFORM-d) delta = 8.06 (dd, J=0.8, 6.1 Hz, 2H). (0333) [0167] Note that the hemiacetal hydrate can be detected in the 1H NMR as a doublet at delta = (0334) 7.69. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In toluene; at 110.0℃;Inert atmosphere; | 5-bromo-1 ,3-dichloro-2-fluorobenzene (1 .00 equivalents), bis(pinacolato)diboron (1 .30 equivalents), Pd(dppf)Cl2 (0.05 equivalents) and potassium acetate (2.50 equivalents) are stirred under nitrogen atmosphere in toluene at 1 10 C until completion of the reaction (monitoring with GC/MS, usually finished within 4-16 h). Active carbon and Celite (kieselguhr) are added to the reaction mixture and stirred at 100 C for 10 minutes. Subsequently, the mixture is hot filtered and concentrated under reduced pressure. The obtained crude product is purified via column chromatography using a cyclohexane/ dichloromethane mixture (1 :1 ), giving E1 as solid (78 %). |
78% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In toluene; at 110.0℃;Inert atmosphere; | 5-bromo-1 ,3-dichloro-2-fluorobenzene (1 .00 equivalents), bis(pinacolato)diboron (1 .30 equivalents), Pd(dppf)Cl2 (0.05 equivalents) and potassium acetate (2.50 equivalents) are stirred under nitrogen atmosphere in toluene at 1 10 C until completion of the reaction (monitoring with GC/MS, usually finished within 4-16 h). Active carbon and Celite (also known as diatomaceous earth or kieselgur) are added to the reaction mixture and stirred at 100 C for 10 minutes. Subsequently, the mixture is hot filtered and concentrated under reduced pressure. The obtained crude product is purified via column chromatography using a cyclohexane/ dichloromethane mixture (1 :1 ), giving E1 as solid (78 %). AAV1 (78% yield), wherein 5-bromo-1 ,3-dichloro-2-fluorobenzene (CAS 17318-08-0) and bis(pinacolato)diboran (CAS 73183-34-3) were used as reactants |
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