Structure of 191595-63-8
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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. : | 191595-63-8 |
Formula : | C7H4F3NO3 |
M.W : | 207.11 |
SMILES Code : | O=C(O)C1=C(O)N=C(C(F)(F)F)C=C1 |
MDL No. : | MFCD01862657 |
InChI Key : | JPOIZUVDMRHIIT-UHFFFAOYSA-N |
Pubchem ID : | 2775116 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 7.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 38.22 |
TPSA ? Topological Polar Surface Area: Calculated from |
70.42 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.83 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.66 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.2 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.33 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.46 |
Solubility | 0.715 mg/ml ; 0.00345 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.93 |
Solubility | 0.244 mg/ml ; 0.00118 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.72 |
Solubility | 3.97 mg/ml ; 0.0192 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) |
No |
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 |
-6.26 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 |
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) |
1.68 |
* 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 |
---|---|---|
40% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 70℃; for 2.0h; | Preparation of Reagent 3-(chloromethyl)-2-methoxy-6-(trifluoromethyl)pyridine; A. Preparation of methyl 2-methoxy-6-(trifluoromethyl)nicotinate; To a stirring solution of <strong>[191595-63-8]2-hydroxy-6-(trifluoromethyl)nicotinic acid</strong> (2.07 g, 10 mmol) in anhydrous DMF (15 mL) at room temperature was added iodomethane (3.1 mL, 50 mmol), followed by anhydrous K2CO3 (4.15 g, 30 mmol). The resulting suspension was stirred at 70 C. for 2 h. Analysis by HPLC/MS indicated the starting acid had been consumed. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (50 mL×3). The combined EtOAc extracts were washed with saturated aqueous NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (40 g) eluted with a gradient of ethyl acetate (0-100%) in hexanes to afford 950 mg (40%) of the title compound. HPLC/MS: retention time=3.17 min, [M+H]+=236.3. |
40% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 70℃; for 2.0h; | A. Preparation of methyl 2-methoxy-6-(trifluoromethyl)nicotinate To a stirring solution of <strong>[191595-63-8]2-hydroxy-6-(trifluoromethyl)nicotinic acid</strong> (2.07 g, 10 mmol) in anhydrous DMF (15 mL) at room temperature was added iodomethane (3.1 mL, 50 mmol), followed by anhydrous K2CO3 (4.15 g, 30 mmol). The resulting suspension was stirred at 70 C. for 2 h. Analysis by HPLC/MS indicated the starting acid had been consumed. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (50 mL*3). The combined EtOAc extracts were washed with saturated aqueous NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (40 g) eluted with a gradient of ethyl acetate (0-100%) in hexanes to afford 950 mg (40%) of the title compound. HPLC/MS: retention time=3.17 min, [M+H]+=236.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; at 0 - 70℃; for 15.08h; | Step C:; A solution of compound V-3 (5.89 g, 28.44 mmol) in MeOH (60 mL) was cooled in an ice bath, then H2SO4 (Cone, 5 mL) was added dropwise over 5 minutes. The resulting reaction mixture was heated at 700C for 15 hours, then the solvent was removed and the resulting residue was partitioned between water (100 mL) and ethyl acetate (200 mL). The organic layer was separated and aqueous layer was extracted with ethyl acetate (3x100 mL). The combined organic phases were washed with water, brine, dried over MgSO4, filtered and concentrated to give compound V-4 (m/z (ES) (M+H)+= 222), which was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; water; at 103℃; for 2.0h; | Step B:; A mixture of compound V-2 (5.87 g, 28.48 mmol) and concentrated HCl (50 mL) was heated to 1030C for 2 hours, then concentrated and the resulting residue V-3 (m/z (ES) (M+H)+= 208) was used in the next step without further purification. |
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