Structure of 372120-55-3
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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. : | 372120-55-3 |
Formula : | C8H4BrF3O |
M.W : | 253.02 |
SMILES Code : | O=CC1=CC=C(C(F)(F)F)C(Br)=C1 |
MDL No. : | MFCD13185384 |
Boiling Point : | No data available |
InChI Key : | MWYYNBYTVFKXSD-UHFFFAOYSA-N |
Pubchem ID : | 11482172 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.53 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.82 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.96 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.43 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.68 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.22 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.48 |
Solubility | 0.0832 mg/ml ; 0.000329 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.98 |
Solubility | 0.264 mg/ml ; 0.00104 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.09 |
Solubility | 0.0206 mg/ml ; 0.0000815 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-5.74 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 |
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 |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.55 |
* 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 manganese dioxide; In chloroform; | EXAMPLE 63B 3-bromo-4-(trifluoromethyl)benzaldehyde The product from Example 63A in chloroform (100 mL) was treated with manganese dioxide (1.1 g, 12.6 mmol) and stirred overnight. The mixture was filtered and the filtrate was concentrated. The residue was chromatographed on silica gel eluding with 15% ethyl acetate/hexanes to rovide the title compound (0.28 g). 1H NMR (CDCl3) delta 7.9 (m, 2H), 8.2 (s, 1H), 10.02 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | To a solution of a 60% dispersion of NaH in mineral oil (0.31 g, 7.75 mmol) in DME (2 mL) at - 30 C was added a solution of ethyl 2-phosphonoacetate (1.46 mL, 7.29 mmol) in DME (13 mL), and the mixture was stirred at this temperature for 30 min. To this solution was added a solution of <strong>[372120-55-3]3-bromo-4-(trifluoromethyl)benzaldehyde</strong> (44) (1.68 g, 6.63 mmol) in DME (3 mL), and the reaction was stirred at -30 C for 1.5 h and then poured into water (50 mL) and extracted with ethyl acetate. The combined organic layers were washed with an aqueous saturated NH4C1 solution and then brine, dried over sodium sulfate, filtered and concentrated in vacuo to give a crude product that was purified by column chromatography (150 mL Si02, ethyl acetate :hexanes 5:95) to give 45 (2.1 188 g, 98%) as a colorless crystalline solid: 1H NMR (400 MHz, CDC13) ? 7.84 (s, 1H), 7.69 (d, J= 8.0, 1H), 7.59 (d, J= 16.0, 1H), 7.52 (d, J= 8.0, 1H), 6.50, (d, J= 16.0, 1H), 4.27 (q, J= 7.2, 2H), 1.34 (t, J= 7.2, 3H); 13C NMR (100.6 MHz, CDC13) ? 165.9, 141.0, 139.2, 133.8, 131.4, 130.7, 130.4, 128.3, 128.2, 128.1, 128.1, 126.4, 123.9, 122.2, 121.2, 120.6, 120.5, 60.9, 14.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; diethyl ether; for 0.5h;Cooling with ice; | Step 1 (0506) To a mixture of <strong>[372120-55-3]3-bromo-4-trifluoromethylbenzaldehyde</strong> (2 g) and tetrahydrofuran (36 mL) was added methylmagnesium iodide (2 mol/L diethylether solution, 4.35 mL) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes. The mixture was diluted with ammonium chloride aqueous solution and ethyl acetate. The ethyl acetate layer was washed with brine, and concentrated under reduced pressure to give 1-(3-bromo-4-trifluoromethylphenyl-ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 85℃;Inert atmosphere; | A 250-mL round-bottom flask was charged with <strong>[372120-55-3]3-bromo-4-(trifluoromethyl)benzaldehyde</strong> (3.00 g, 1 1.9 mmol, 1.00 equiv), 2,2'-bis(diphenylphosphino)- l, l'-binaphthyl (1.1 1 g, 1.78 mmol, 0.15 equiv), cesium carbonate (1 1.6 g, 35.6 mmol, 3.00 equiv), tris(dibenzylideneacetone)dipalladium (0.545 g, 0.600 mmol, 0.05 equiv), toluene (60 mL), and morpholine (1.55 g, 17.8 mmol, 1.50 equiv) under nitrogen. The resulting solution was stirred overnight at 85 C and quenched with water (80 mL). The resulting solution was extracted with EtOAc (2 x 150 mL) and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 2.00 g (65% yield) of 3-morpholino-4- (trifluoromethyl)benzaldehyde as a yellow solid. LCMS (ESI, m/z): 260 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine; at 100℃; | A 250-mL round-bottom flask was charged with 3-bromo-4- (trifluoromethyl)benzaldehyde (3.00 g, 11.9 mmol, 1.00 equiv), MeOH (50 mL), 1,1?- bis(diphenylphosphino)ferrocenepalladiumdichloride (870 mg, 1.19 mmol, 0.10 equiv), and triethylamine (3.61 g, 35.7 mmol, 3.00 equiv). Carbon monoxide (10 atm) was introduced. The resulting solution was stirred overnight at 100 C and quenched with water (50 mL). The resulting solution was extracted with EtOAc (2 x 80 mL) and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 2.20 g (80% yield) of methyl 5- formyl-2-(trifluoromethyl)benzoate as an off-white semi-solid. ?H NIVIR (400 MHz, Chloroform-cl) oe 10.1 (s, 1H), 8.31 (s, 1H), 8.12 - 8.15 (m, 1H), 7.97 (d, J= 8.0 Hz, 1H), 4.00 (s, 3H). |
80% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine; at 100℃; | Example 178: 1,1,1,3,3,3-Hexafluoropropan-2-yl 1-(3-carbamoyl-4-(trifluoromethyl)benzyl)- 1,8-diazaspiro[4.5]decane-8-carboxylate Step 1: Synthesis of methyl 5-formyl-2-(trifluoromethyl)benzoate A flask was charged with <strong>[372120-55-3]3-bromo-4-(trifluoromethyl)benzaldehyde</strong> (3.00 g, 11.9 mmol, 1.00 equiv), MeOH (50 mL), 1,1'-bis(diphenylphosphino)ferrocenepalladiumdichloride (870 mg, 1.19 mmol, 0.10 equiv), and TEA (3.61 g, 35.7 mmol, 3.00 equiv). Carbon monoxide (10 atm) was introduced, and the reaction was stirred overnight at 100 C before quenching with water (50 mL). The resulting solution was extracted with EtOAc (2 x 80 mL) and the organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was chromatographed on a silica gel column with EtOAc/petroleum ether (8/92) to provide 2.2 g (80% yield) of methyl 5-formyl-2-(trifluoromethyl)benzoate as an off-white semi-solid.1H NMR (400 MHz, Chloroform-d) ^ 10.1 (s, 1H), 8.31 (s, 1H), 8.12- 8.15 (m, 1H), 7.97 (d, J = 8.0 Hz, 1H), 4.00 (s, 3H). |
73% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine; at 65℃; under 11400.8 Torr;Autoclave; | A 100-mL autoclave was charged with <strong>[372120-55-3]3-bromo-4-(trifluoromethyl)benzaldehyde</strong> (3.00g, 11.9 mmol, 1.00 equiv), 1,1?-bis(diphenylphosphino)ferrocenepalladiumdichloride (0.869 g,1.19 mmol, 0.10 equiv), triethylamine (3.61 g, 35.7 mmol, 3.00 equiv), and methanol (50 mL). The contents of the autoclave were placed under an atmosphere of carbon monoxide (15 atm). The resulting solution was stirred overnight at 65 C and quenched with water (50 mL). The reaction mixture was extracted with dichloromethane (3 x 50 mL) and the organic layers were combined, washed with brine (1 x 100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 2.00 g (73% yield) of methyl 5-formyl-2-(trifluoromethyl)benzoate. ?H NMR (300 MHz, Chloroform-cl) oe 10.4 (s, 1H), 8.31 (s, 1H), 8.14 (d, J 8.1 Hz, 1H), 7.97 (d, J 8.1 Hz, 1H), 4.01 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere; | A 50-mL round-bottom flask was charged with 3-bromo-4- (trifluoromethyl)benzaldehyde (1 .00 g, 3.95 mmol, 1.00 equiv), tert-butyl 4-(tetramethyl- 1,3,2- dioxaborolan-2-yl)- 1,2,3 ,6-tetrahydropyridine- 1 -carboxylate (1.84 g, 5.95 mmol, 1.50 equiv), tetrakis(triphenylphosphine)palladium (230 mg, 0.198 mmol, 0.05 equiv), potassium carbonate (1.64 g, 11.9 mmol, 3.00 equiv), 1,4-dioxane (10 mL), and water (2 mL) under nitrogen. The resulting solution was stirred overnight at 80 C and quenched with water (10 mL). The mixture was extracted with dichloromethane (3 x 10 mL) and the organic layers were combined, washed with brine (2 x 10 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/4) to provide 1.00 g (71% yield) of tert-butyl 4-(5-formyl-2- (trifluoromethyl)phenyl)-3 , 6-dihydropyridine- 1 (2H)-carboxylate as yell ow oil. LCMS (ESI, m/z): 356 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | j00219J A vial was charged with DCE (10 mL), <strong>[372120-55-3]3-bromo-4-(trifluoromethyl)benzaldehyde</strong> (252 mg, 1.00 mmol, 1.00 equiv), t-butyl 4-amino-4-methylpiperidine-1-carboxylate (214 mg, 1.00 mmol,1.00 equiv), and triethylamine (303 mg, 2.99 mmol, 3.00 equiv). The resulting solution was stirred for 1 h at room temperature, then sodium triacetoxyborohydride (636 mg, 3.00 mmol, 3.00 equiv) was added. The mixture was stirred overnight at room temperature and quenched with water (10 mL), as described in Example 1, Step 6. The residue was chromatographed on a silica gel column to provide 300 mg (67% yield) of t-butyl 4-((3-bromo-4-(trifluoromethyl)benzyl)amino)-4- methylpiperidine-1-carboxylate as a yellow oil. LCMS (ESI, m/z): 451 [M+H]. |
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