Structure of 954815-11-3
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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. : | 954815-11-3 |
Formula : | C8H4F3IO2 |
M.W : | 316.02 |
SMILES Code : | O=C(O)C1=CC=C(I)C=C1C(F)(F)F |
MDL No. : | MFCD09881756 |
Boiling Point : | No data available |
InChI Key : | XSQLEPZNGCNYKF-UHFFFAOYSA-N |
Pubchem ID : | 17733364 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 51.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.98 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.16 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.52 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.23 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.1 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.86 |
Solubility | 0.0434 mg/ml ; 0.000137 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.43 |
Solubility | 0.118 mg/ml ; 0.000374 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.59 |
Solubility | 0.0814 mg/ml ; 0.000258 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 |
-6.11 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 |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
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) |
1.91 |
* 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 |
---|---|---|
A solution of sodium nitrite (0.37 g, 5.36 mmol) in water (1.5 mL) was added dropwise to a cooled (0 C.) suspension of 4-amino-2-(trifluoromethyl)benzoic acid (1 g, 4.9 mmol) in hydrochloric acid (37%, 2 mL) and ice (3 g). After 20 min at 0 C. the reaction mixture was slowly added to a stirred solution of potassium iodide (8.09 g, 48.8 mmol) in water (8 mL) at 0 C. The resulting mixture was stirred at room temperature over night, dichloromethane and sodium sulfite (2.52 g, 20.0 mmol) was added, the organic phase was collected, dried over magnesium sulfate and the solvent was evaporated to give the title compound.1H NMR (DMSO-d6) delta ppm 13.78 (s, 1H) 8.11-8.24 (m, 2H) 7.49-7.66 (m, 1H); MS (ESI) m/z 315 [M-1]-. | ||
A solution of sodium nitrite (0.37 g, 5.36 mmol) in water (1.5 mL) was added dropwise to a cooled (0 0C) suspension of 4-amino-2-(trifluoromethyl)benzoic acid (1 g, 4.9 mmol) in hydrochloric acid (37%, 2 mL) and ice (3 g). After 20 min at 0 0C the reaction mixture was slowly added to a stirred solution of potassium iodide (8.09 g, 48.8 mmol) in water (8 mL) at 0 0C. The resulting mixture was stirred at room temperature over night, dichloromethane and sodium sulfite (2.52 g, 20.0 mmol) was added, the organic phase was collected, dried over magnesium sulfate and the solvent was evaporated to give the title compound. 1H NMR (DMSO-J6) delta ppm 13.78 (s, 1 H) 8.11 - 8.24 (m, 2 H) 7.49 - 7.66 (m, 1 H); MS (ESI) m/z 315 [M-I]". | ||
Intermediate 31 : 4-lodo-2-(trifluoromethyl)benzoic acid; To a suspension of 4-amino-2-(trifluoromethyl) benzoic acid (10 g, 48.7 mmol, Apollo) in water (43 ml) in an ice-water bath (internal temperature at 5 0C) was added concentrated sulphuric acid specific gravity 1.84 (7 ml_, 131 mmol). To the slight suspension was added a solution of sodium nitrite, super free flowing (3.76 g, 54.5 mmol, Aldrich) in ice cold water (20 ml) dropwise. The suspension was stirred in an ice-water bath for 20 min. To the mixture was added a solution of potassium iodide, extra pure briquettes (12.14 g, 73.1 mmol, Acros) in ice cold 1 M sulphuric acid (30 ml). The mixture was allowed to warm to ambient temperature and then heated to 800C for 45 min under nitrogen. The mixture was allowed to cool to ambient temperature. The mixture was partitioned between ethyl acetate (300 ml) and water(300 ml). The phases were separated and the organic phase washed with brine (50 ml x 2), dried (MgSO4), filtered and the solvent removed in vacuo to give the title compound as a dark brown solid (16.7 g); LCMS: (System 4) (M-H)" = 315, tREtau =2.64 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of <strong>[954815-11-3]4-iodo-2-(trifluoromethyl)benzoic acid</strong> (for a preparation see Intermediate 31 )(16.7 g, 52.8 mmol) in THF (150 ml) at ambient temperature under nitrogen was added 1.0 M borane-tetrahydrofuran complex (100 ml, 100 mmol, Aldrich) dropwise. The solution was heated to 80 0C for 1.5 h. To the solution at ambient temperature was added methanol (75 ml) and then heated to 80 0C for 1 h. The solvent was removed in vacuo to leave a mobile oil. The residue was partitioned between ethyl acetate (200 ml) and 2 N aqueous HCI (100 ml). The phases were separated and the organic phase washed with 2 N aqueous sodium hydroxide (100 ml), brine (50 ml), then dried (MgSO4), filtered and the solvent removed in vacuo to give [4-iodo-2-(trifluoromethyl)phenyl]methanol as a pale brown solid (14.8 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With triethylamine; triphenylphosphine;palladium diacetate; In N,N-dimethyl-formamide; at 100℃; for 5.0h;Inert atmosphere; | Under argon, first 3.34 g (7.90 mmol) of N-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-acrylamide from Example 2, Stage 1, and then 2.49 g (7.90 mmol) of <strong>[954815-11-3]4-iodo-2-(trifluoromethyl)benzoic acid</strong> (commercially available, CAS Registry Number: 954815-11-3), 0.206 g (7.90 mmol) of triphenylphosphine, 88.4 mg (0.39 mmol) of palladium(II) acetate and 13.5 g (133 mmol) of triethylamine were initially charged in 67 ml of N,N-dimethylformamide, and the reaction mixture was stirred at 100 C. for 5 hours. After addition of water, the solution was extracted with ethyl acetate, and then the organic phase was washed three times with saturated sodium chloride solution and dried over sodium sulphate. The solvent was distilled off under reduced pressure and the residue was chromatographed on silica gel with ethyl acetate.Yield: 2.57 g (60% of theory).1H NMR (400 MHz, d6-DMSO) delta=6.10 (m, 1H), 6.93 (d, 1H), 7.6 (m, 1H), 7.69 (m, 1H), 7.75 (m, 2H), 7.85 (m, 1H), 7.95 (m, 1H), 7.99 (m, 1H), 9.38 (d, 1H).HPLC-MS: logP=3.29; mass (m/z): 486.0 (M+H)+.In analogy to the method described in Synthesis Example 2, Stage 2, the following compounds of the general formula (I-5) were also obtained: |
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