Structure of 384-16-7
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CAS No. : | 384-16-7 |
Formula : | C7H3BrClF3 |
M.W : | 259.45 |
SMILES Code : | FC(C1=C(Br)C(Cl)=CC=C1)(F)F |
MDL No. : | MFCD00673988 |
Boiling Point : | No data available |
InChI Key : | GMUWNTUONIQRFP-UHFFFAOYSA-N |
Pubchem ID : | 17750574 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.31 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.27 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.66 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.35 |
Solubility | 0.0115 mg/ml ; 0.0000442 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.84 |
Solubility | 0.0378 mg/ml ; 0.000146 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.75 |
Solubility | 0.00456 mg/ml ; 0.0000176 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 |
No |
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) |
Yes |
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 |
-4.95 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 |
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) |
1.5 |
* 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 |
---|---|---|
With tri-tert-butyl phosphine; tetrabutylammomium bromide; palladium diacetate; potassium carbonate; In N,N-dimethyl-formamide; toluene; at 150℃; for 1.5h;Microwave irradiation; | To a microwave vial were added tert-butyl 4-(4-(l-(phenylsulfonyl)-3-vinyl-lH- pyrrolo[2,3-b]pyridin-5-yl)-lH-pyrazol-l-yl)piperidine-l-carboxylate (1.07 g, 2.0 mmol), 2- bromo-l-chloro-3-(trifluoromethyl)benzene (780 mg, 3.0 mmol), Pd(OAc)2 (9 mg, 40 mumol), TBAB (650 mg, 2.0 mmol), K2C03 (930 mg, 6.0 mmol), DMF (10 mL) and P(t-Bu)3 (36 mg, 74 umol, 1 M in toluene). The mixture was stirred and microwaved at 150 C for 90 minutes, then cooled to rt, washed with brine (150 mL) and extracted with DCM (150 mL x 3). The combined organic layers were washed with brine (100 mL x 2), dried over anhydrous Na2S04, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v) = 4/1) to give the PhS02-protected product (purity: 88%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | To a solution of <strong>[384-16-7]2-bromo-1-chloro-3-(trifluoromethyl)benzene</strong> (29, 2.45 g, 9.5 mmol) in dry THF (75 mL) at -78 C was added dropwise n-BuLi (4 mL,10 mmol) over 1 h under N2. The slurry was stirred at -78 C for 45 min, then a solution of the diethyl oxalate(1.46 g, 10 mmol) in THF (25 mL) was added dropwise over 1 h at -78 C and the mixture was stirred at -78 C for 45 min. The cooling bath was removed, and the temperature was allowed to rise to-20 C. A solution of NH4Cl (4 g) in water (75 mL) was then added over 5 min and the resulting mixture was concentrated under reduced pressure. The residue was partitioned between EtOAc (75 mL) andbrine (30 mL). The organic phase was separated, washed with brine (50 mL), dried and concentrated under reduced pressure to afford the title compound as a brown oil (2.5 g, 95%). LCMS (ESI): m/z = 298.0 [M+18]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In methanol; water; toluene; at 90℃; | A mixture o met y , - - - - , , , -tetramethyl-1,3,2-dioxaborolan-2- yl)prop-1-en-1-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)propanoate (1 g, 2.58 mmol), 2- bromo-1-chloro-3-(trifluoromethyl)benzene (1 g, 3.85 mmol), sodium carbonate (800 mg, 7.48 mmol), tetrakis(triphenylphosphine)palladium(0) (300 mg, 0.26 mmol), toluene (20 mL), methanol (10 mL) and water (5 mL) was stirred overnight at 90 C. The mixture was diluted with water, and extracted twice with dichloromethane. The combined organic layers were dried (Na2SO4) and concentrated. The resulting residue was purified via MPLC eluting with 20% ethyl acetate in petroleum ether to afford methyl (S,E)-3-(6-(2-(2-chloro-6- (trifluoromethyl)phenyl)prop-1 -en-1-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)propanoate (250 mg, 22%) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tri-tert-butyl phosphine; tetrabutylammomium bromide; palladium diacetate; potassium carbonate; In N,N-dimethyl-formamide; toluene; at 150℃; for 1.5h;Microwave irradiation; | The compound 4 - (4 - (1 - (phenyl-sulfonyl) -3 - vinyl - 1H - pyrrolo [2, 3 - b] pyridine -5 - yl) - 1H - pyrazole -1 - yl) piperidine -1 - carboxylic acid tert-butyl ester (1.07 g, 2.0 mmol), 2 - bromo -1 - chloro -3 - (trifluoromethyl) benzene (780 mg, 3.0 mmol), Pd (OAc)2 (9 Mg, 40 mumol), TBAB (650 mg, 2.0 mmol), K2 CO3 (930 Mg, 6.0 mmol), DMF (10 ml) and P (t - Bu)3 (36 Mg, 74 mumol, 1 M toluene solution) are sequentially placed in the microwave in the bottle, the mixture under microwave conditions, for 150 C stirring for 90 minutes, cooled to the room temperature, and then the salt water (150 ml) washing, for DCM (150 mLx 3) extraction, the combined organic phase for salt water (100 ml x 2) washing, anhydrous Na2 SO4 Drying, concentrated under reduced pressure, the residue by silica gel column chromatography (PE/EtOAc (v/v)=4/1) purified PhSO2 Protection of the product (HPLC: 88%). The upper step of the obtained compounds are dissolved in EtOH (40 ml) in, then to the reaction solution is added in an aqueous solution of NaOH (20 ml, 10%), the reaction liquid 90 C stirring for 1.5 hours, cooling to room temperature, concentrated under reduced pressure, the residual aqueous phase for EtOAc (50 ml x 3) extraction. The combined organic phase with anhydrous Na2 SO4 Drying, concentrated under reduced pressure, the residue by silica gel column chromatography (PE/EtOAc (v/v)=1/1) to obtain the title compound as yellow solid (270 mg, 24%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71 mg | Under nitrogen substitution,2-Bromo-3-chlorobenzotrifluoride (212 mg)Of tetrahydrofuran (0.7 mL)Was added isopropyl magnesium chloride / lithium chloride complex / tetrahydrofuran solution (1.3 M, 0.63 mL) dropwise at room temperature and stirred for 1 hour.This solution was added to the ice-cooled compound (172 mg) obtained in Example 46c,In diethyl ether (3 mL) over 5 minutes.Thereafter, the mixture was stirred under ice-cooling for 2 hours and at room temperature for 2.5 hours.Since the reaction was not completed,Again <strong>[384-16-7]2-bromo-3-chlorobenzotrifluoride</strong> (212 mg),From isopropyl magnesium chloride / lithium chloride complex / tetrahydrofuran solution (1.3 M, 0.63 mL)Grignard reagent was prepared by the same operation as above,Was added dropwise to the ice-cooled reaction solution over 5 minutes.After stirring for 1 hour under ice cooling, 0.5N hydrochloric acid was added and the mixture was extracted with ethyl acetate.The extract layer was washed successively with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine,After drying with anhydrous sodium sulfate and filtration, the solvent was distilled off under reduced pressure.The obtained residue was purified by silica gel column chromatography (ethyl acetate / hexane) to obtain the title compound (71.0 mg) as a colorless transparent gummy solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.22 g | 2-Bromo-1-chloro-3-trifluoromethylbenzene (2.49 g)In tetrahydrofuran (25 mL) at -78 C.,n-Butyllithium (1.58 N hexane solution, 6.10 mL) was added,And the mixture was stirred at the same temperature for 30 minutes.Then, the obtained lithio compoundAt -78 C.,Imidazo [1,5-a] pyridine-3-carboxaldehyde (700 mg) in tetrahydrofuran (25 mL), and the mixture was stirred at -78 C. for 1 hour. Water was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic layer was dried over magnesium sulfate, concentrated under reduced pressure, and then purified by silica gel column chromatography (ethyl acetate / hexane) to obtain the title compound (1.22 g) as a pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Lithium 2,2,6,6-tetramethylpiperidin-1-ide (2.84 g, 19.27 mmol) was placed in an oven-dried 250-mL round-bottomed flask in a glovebox and removed. Diethyl ether (75 mL) was added and the solution was cooled to -78 C (reaction mixture is not homogeneous). 2-Bromo-1-chloro-3-(trifluoromethyl)benzene (5.00 g, 19.3 mmol, 1.0 equiv) was added as solution in ether (25 mL) dropwise over 10 minutes and the mixture was allowed to stir at -78 C for 1 hour. 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.9 mL, 19.27 mmol, 1.0 equiv) was then added to the non-homogeneous reaction mixture over 10 minutes and the reaction was allowed to warm slowly to room temperature overnight. The reaction was quenched with saturated NH4C1 at 0 C and warmed to room temperature, layers separated. The aqueous was further extracted with diethyl ether (2) and the combined organics dried over sodium sulfate, filtered and concentrated. Purification over silica gel using a 0 to 5% ethyl acetate/hexane gradient afforded the title compound (3.87 g, 52% yield) as a viscous yellow oil. |
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