Structure of 40161-54-4
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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.
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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 40161-54-4 |
Formula : | C7H3BrF4 |
M.W : | 243.00 |
SMILES Code : | FC(C1=CC=C(Br)C(F)=C1)(F)F |
MDL No. : | MFCD00042497 |
InChI Key : | XCTQZIUCYJVRLJ-UHFFFAOYSA-N |
Pubchem ID : | 142414 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.1 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.29 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.6 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.18 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.51 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.95 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.92 |
Solubility | 0.0293 mg/ml ; 0.000121 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.29 |
Solubility | 0.126 mg/ml ; 0.000517 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.42 |
Solubility | 0.00922 mg/ml ; 0.0000379 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 |
-5.23 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<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 |
---|---|---|
1.68 g | Example 41 : N-(5-Fluorothiazol-2-yl)-5-(2-(4-methylpiperazin-l-yl)-4- (trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(lH)-sulfonamide Step 1 : tert-Butyl 5-(2-(4-methylpiperazin-l-yl)-4-(trifluoromethyl)phenyl)-3,4- dihydroisoquinoline-2(lH)-carboxylate A microwave vial charged with 1 -methylpiperazine (2.74 ml, 24.69 mmol) and 1- bromo-2-fluoro-4-(trifluoromethyl)benzene (2.000 g, 8.23 mmol) was heated to 180 C in a microwave reactor for 90 minutes. The reaction mixture was concentrated then transferred to a vial charged with Cl2Pd(AmPhos) (Sigma- Aldrich, St. Louis, MO, 0.291 g, 0.412 mmol), tert-butyl 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(lH)- carboxylate (ASW Medchem, Brunswick, NJ, 2.96 g, 8.23 mmol), and potassium phosphate (8.74 g, 41.2 mmol). 8 mL dioxane and 4 mL water were added, and the reaction mixture was heated to 120 C for 2 hours. After cooling to rt, the reaction mixture was poured into water and extracted with DCM. The organics were concentrated then purified by reverse phase column chromatography [RediSep Gold CI 8 150g, 15 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] yielding tert-butyl 5-(2-(4-methylpiperazin-l-yl)-4- (trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(lH)-carboxylate (1.68g, 3.53 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 120℃; for 72h; | Intermediate M: 5-(2-Fluoro-4-(trifluoromethyl)phenyl)-l,2,3,4- tetrahydroisoquinoline hydrochloride A solution of Pd(PPh3)4 (Strem Chemicals Inc., Newburyport, MA, 0.643 g, 0.557 mmol), l-bromo-2-fluoro-4-(trifluoromethyl)benzene (1.353 g, 5.57 mmol), tert-butyl 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline- 2(lH)-carboxylate (ASW Medchem, Brunswick, NJ, 2.000 g, 5.57 mmol), and potassium carbonate (3.08 g, 22.27 mmol) in 12 mL dioxane and 6 mL water was heated to 120 C for 3 days. The reaction mixture was diluted with diethyl ether, washed with water, the organics dried over MgS04 and concentrated to provide tert- butyl 5-(2-fluoro-4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(lH)- carboxylate. The resulting residue was dissolved in 10 mL THF and was treated with HCI 4 N in dioxane (9.74 ml, 39.0 mmol), and allowed to stir at room temperature overnight. The reaction mixture was diluted with diethyl ether/heptane, and the resulting solid was filtered and dried yielding 5-(2-fluoro-4-(trifluoromethyl)phenyl)- 1,2,3,4-tetrahydroisoquinoline hydrochloride (1.930 g, 5.82 mmol). [M+H]+ = 296.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.6 g | tert-Butyllithium (21.8 mL, 1.7M in pentane, 37.0 mmol) was added dropwise to 4-bromo-3-fluorobenzotrifluoride (5.00 g, 20.58 mmol) in THF (50 mL) at ?70° C. After 1 h, 3-oxotetrahydrofuran (1.78 g, 20.58 mmol) in THF was added dropwise. The reaction mixture was warmed to ?10° C. mixture and quenched with NH4Cl satured solution. Ethyl acetate was added, the organic layer was separated, dried over sodium sulfate and evaporated. The crude obtained was purified by flash chromatography (eluent: cyclohexane/AcOEt; gradient from 0percent to 80percent of AcOEt) to obtain 1.6 g of the 3-(2-fluoro-4-trifluoromethyl-phenyl)-tetrahydro-furan-ol.GC-MS (Method 9): Rt=7.58 minGC-MS (Method 9): Rt=7.58 min |
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