Structure of 772-49-6
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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. : | 772-49-6 |
Formula : | C7H4ClF3O |
M.W : | 196.55 |
SMILES Code : | FC(F)(F)OC1=CC(Cl)=CC=C1 |
MDL No. : | MFCD00276971 |
Boiling Point : | No data available |
InChI Key : | OLDJEKBXICPMAS-UHFFFAOYSA-N |
Pubchem ID : | 2777270 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338-P304+P340-P405-P501 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.14 |
TPSA ? Topological Polar Surface Area: Calculated from |
9.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.28 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.19 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.5 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.03 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.38 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.94 |
Solubility | 0.0228 mg/ml ; 0.000116 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.09 |
Solubility | 0.0159 mg/ml ; 0.0000807 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.64 |
Solubility | 0.0446 mg/ml ; 0.000227 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 |
-4.52 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.73 |
* 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 |
---|---|---|
In 1,2-dichlorotrifluoroethyl-trifluoromethylether; at -40℃;Inert atmosphere; | General procedure: The procedure consists of bubbling a stream of hypofluorite (5.5 NL/h: He = 80%, FTM = 18.5%, COF2 = 1.5%) into a solution of the aromatic compounds maintained at the desired temperature (-30 C; -80 C) in a semi-batch method [57].The solubility of the aromatic compounds was measured by carrying out a cloud-point measurement in selected solvents. All the aromatics tested (alpha,alpha,alpha-trifluoro-toluene, toluene, benzene, chloro-benzene, methoxybenzene) are soluble at concentrations between 4% and 5% in the chloro-fluoro-ether (CF3OCFClCF2Cl) used as reaction solvent.A cylinder containing 150 ml of a diluted (3%) solution of the aromatic substrate in 1,2-dichlorotrifluoroethyl-trifluoromethyl-ether (CF3OCFClCF2Cl) was prepared at room temperature. This solution was then poured in the 250 ml stainless steel stirred reactor, cooled at -40 C and then stripped with helium for 15 min to eliminate the dissolved air since oxygen strongly interacts with radical based mechanisms.Subsequently the hypofluorite stream was bubbled in the reactor kept at -40 C under vigorous mechanical stirring. For one mole of aromatic substrate only 0.05-0.88 mol of hypofluorite were added, obtaining only a partial conversion of the aromatics. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | N,N-Di-isopropylamine (38.4 ml, 27lmmol) was added dropwise to a solution of nbutyllithium (1.6 M, 169 ml, 271 mmol) in THF (180 ml) at 0C and the reaction mixture was stirred and allowed to warm to room temperature over 30 mins. The LDA solution was then added drop wise over lOminutes to a solution of 1-chloro-3- (trifluoromethoxy)benzene (50 g, 246 mmol) in THF (500 ml) at -70C and the resultingmixture was stirred at -70C for 30 minutes. Finally N,N-dimethylformamide (23 ml, 296 mmol) was added dropwise and the resultant mixture stirred at -70C for 30 minutes.The reaction was quenched at -70C by addition of NH4C1 (saturated aqueous solution) to pH 7-8 and the resulting mixture was extracted with EtOAc (3 x 75 ml). The combined organic phases were washed with water (100 ml), brine (100 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound (55 g, 99% yield).LCMS (Method 16, ES+) RT 1.32 mm., 224 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | To a cooed (-78 C) soution of 1-choro-3-(trifluoromethoxy)benzene (100 g, 510 mmo)in THF (500 mL) was added n-butyflithium (2.5 M/hexanes, 205 mL, 510 mmo)dropwise over a period of 10 minutes. Stirring was maintained at -78 C for I h, andthen a soution of iodine (130 g, 510 mmo) in THF (500 mL) was added dropwise at -78C over a period of 30 minutes. After the addition, the temperature was maintained at -78 C for lh and then aflowed to warm to rt and stirred for a tota? of 18h. The reaction mixture was poured into saturated aqueous Na2SO3 and extracted with EtOAc (2 x 1000 mL). The combined organic extracts were dried over Na2SO4 and concentrated in vacuo to give the tifle compound as an oH (159 g, 96% yied). 1H NMR (500 MHz, CDC3) 67.40 (dd, J= 8.1, 1.4 Hz. IH), 7.32 (t, J= 8.1 Hz, IH). 7.16(dt. J= 8.2, 1.4 Hz, IH). | |
85% | To a cooed (-.78 C) souUon of 1-choro-3-(trfluoromethoxy)benzene (20 g, 102 mrno)n THF (100 mL) was added n-butyWthum (2.5 M/hexanes, 41 mL, 102 mmo) dropwseover a period of 10 minutes. Strrng was mantaned at -78C for I h, and then asouDon of odne (26 g, 102 rnrno) n THF (100 mL) was added dropwse at -.78 C overa perod of 30 ninutes. After the add Won, the temperature was niantaned at -78 C for1 h and then aflowed to warm to rt and stirred for a tota of 18 h. The reacton mixturewas poured nto saturated aqueous Na2SO3 and extracted wfth EtOAc (2 x 200 mL). The combined organc extracts were dried over Na2SO4 and concentrated n vacuo to give the tWe compound as an oH (28 g, 85% yed). 1H NMR (500 MHz, CDC3) oe 7.40 (dd, J = 81, 1.4 Hz, IH), 7.32 (t, J = 8.1 Hz, IH), 7.16 (dt, J = 8.2, 1.4 Hz, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; In acetonitrile; at 20℃; for 16h;Glovebox; Irradiation; Sealed tube; Inert atmosphere; | General procedure: In a glovebox, to an oven-dried 20 mL screw cap vial was added 2- (3, 5-bis (trifluoromethyl) phenyl) -4-nitro-l- (trifluoromethoxy) -6- (trifluoromethyl) -lii-benzo [d] imidazole (1) (105 mg, 0.200 mmol, 1.00 equiv) , arene (2.00 mmol, 10.0 equiv) and Ru (bpy) 3 ( REe) 2, (0.0516 mg, 0.0600 pmol, 0.0300 moll) . Then MeCN (1.00 mL, 0.200 M) and a magnetic stir bar were added. The vial was capped and taken out of the glovebox. The reaction mixture was then stirred and irradiated with a 10 W LED (402 nm) at room temperature. After 16 h, an internal standard PhCF3 (5.84 mg, 4.95 pL, 0.04 mmol, 0.200 equiv) was added to the reaction vial, 0.200 mL of the resulting mixture was transferred to a 2 mL vial containing 0.500 mL of CDCI3. After the yield was determined using 19F NMR, the NMR sample was combined with the rest of the reaction mixture and the solvent was removed in vacuo. The crude material was purified by HPLC under noted conditions. The fractions containing the desired product were combined and extracted with CDCI3 (3 1 mL) , dried with magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to furnish the desired product of trifluoromethoxylation . For volatile compounds, after purification by HPLC, the desired product was extracted with 1 mL CDC13 and then directly characterized. The NMR peaks are referring to CH3CN residue signal ^H-NMR: d 1.94, 13C~NMR: 5 118.26, 1.32).2 | |
With tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; In acetonitrile; at 20℃; for 16h;Glovebox; Irradiation; Sealed tube; Inert atmosphere; | General procedure: In a glovebox, to an oven-dried 20 mL screw cap vial was added 3- methyl-4-nitro-l- ( trifluoromethoxy) -6- (trifluoromethyl ) -1H- benzo[d] [1, 2, 3] triazol-3-ium trifluoromethanesulfonate (lb) (98.0 mg, 0.200 mmol, 1.00 equiv), arene (2.00 mmol, 10.0 equiv) and Ru (bpy) 3 (PFe) 2, (1.72 mg, 2.00 pmol, 1.00 mol%). Then MeCN (1.00 mL, 0.200 M) and a magnetic stir bar were added. The vial was capped and taken out of the glovebox. The reaction mixture was then stirred and irradiated with 2 of 10 W LED (Xmax = 447 nm) at room temperature. After 16 h, an internal standard PhCF3 (24.6 pL, 0.200 mmol, 1.00 equiv) was added to the reaction vial, 0.200 mL of the resulting mixture was transferred to a 2 mL vial containing 0.500 mL of CDC13. After the yield was determined using 19F NMR, the NMR sample was combined with the rest of the reaction mixture and the solvent was removed in vacuo. The crude material was purified by HPLC under noted conditions. The fractions containing the desired product were combined and extracted with CDC13 (3 x 10.0 mL) , dried with magnesium sulfate, and filtered unless otherwise noted. The filtrate was concentrated in vacuo to furnish the desired product of trifluoromethoxylation . For volatile compounds, after purification by HPLC, the desired product was extracted with 1 mL CDCI3 and then directly characterized. The NMR peaks are referring to CCN residue signal (1H-NMR : d 1.94, 13C-NMR: d 118.26, 1.32).2 |
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