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Structure of 450-96-4
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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.
4.5
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CAS No. : | 450-96-4 |
Formula : | C7H4ClF3O |
M.W : | 196.55 |
SMILES Code : | FC(F)(F)OC1=CC=CC=C1Cl |
MDL No. : | MFCD03840206 |
Boiling Point : | No data available |
InChI Key : | NZRLCYJRHKUVCV-UHFFFAOYSA-N |
Pubchem ID : | 2782782 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H315-H319-H225 |
Precautionary Statements: | P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅲ |
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 | 38.13 |
TPSA ? Topological Polar Surface Area: Calculated from |
9.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.22 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.89 |
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 |
3.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.75 |
Solubility | 0.0352 mg/ml ; 0.000179 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.78 |
Solubility | 0.0325 mg/ml ; 0.000165 mol/l |
Class? Solubility class: Log S scale |
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 |
-4.74 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) |
1.54 |
* 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 |
---|---|---|
To a solution of 1 -chloro-2-(trifluoromethoxy)benzene (2.54 mmol) in 10 mL THF were added 1.42 mL n-BuLi (2.5 M solution in hexane) at -78C. After 40 min, a solution of iodine (2.8 mmol) in 2.5 mL THF was added and stirring was continued at RT overnight. The reaction was quenched with water under cooling and extracted with EtOAc (3x). The combined organic layers were dried over MgS04 and concentrated in vacuo. Purification by CC (KP-SIL from Biotage) using Hept to Hept/EtOAc (4/1 ) gives the desired compound (in a regioisomeric mixture as the major product) as colorless oil. LC-MS (A): tR = 0.99 min; 1H NMR ((CD3)2SO) δ: 7.98 (dd, 1 H), 7.70 (dd, 1 H), 7.21 (t, 1 H). | ||
With n-butyllithium; iodine; In tetrahydrofuran; hexane; | A.1.5 Synthesis of 2-chloro-1-iodo-3-(trifluoromethoxy)benzene To a solution of 1-chloro-2-(trifluoromethoxy)benzene (2.54 mmol) in 10 mL THF were added 1.42 mL n-BuLi (2.5 M solution in hexane) at -78 C. After 40 min, a solution of iodine (2.8 mmol) in 2.5 mL THF was added and stirring was continued at RT overnight. The reaction was quenched with water under cooling and extracted with EtOAc (3*). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification by CC (KP-SIL from Biotage) using Hept to Hept/EtOAc (4/1) gives the desired compound (in a regioisomeric mixture as the major product) as colorless oil. LC-MS (A): tR=0.99 min; 1H NMR ((CD3)2SO) δ: 7.98 (dd, 1H), 7.70 (dd, 1H), 7.21 (t, 1H). |
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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