Structure of 1108724-32-8
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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. : | 1108724-32-8 |
Formula : | C7H6BrF2N |
M.W : | 222.03 |
SMILES Code : | CC(C1=CN=CC(Br)=C1)(F)F |
MDL No. : | MFCD18254770 |
InChI Key : | WHDYQJPECGZSLP-UHFFFAOYSA-N |
Pubchem ID : | 68669965 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.29 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.7 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.01 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.35 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.69 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.03 |
Solubility | 0.205 mg/ml ; 0.000923 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.26 |
Solubility | 1.22 mg/ml ; 0.00549 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.88 |
Solubility | 0.0293 mg/ml ; 0.000132 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 |
-5.99 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 |
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) |
1.81 |
* 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 |
---|---|---|
92% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; at 100.0℃; for 16.0h;Inert atmosphere; | Add benzophenone imine (215 mg, 1.19 mmol), cesium carbonate (640 mg, 1.96 mmol), (±)-2,2'-bis(diphenylphosphino)-l, -binaphthalene (BINAP, 98 mg, 0.16 mmol), tris(dibenzylideneacetone)dipalladium [Pd2(dba)3, 90 mg, 0.098 mmol] to the solution of 3-bromo-5-(l, 1 -difluoroethyl)pyridine (200 mg, 0.9 mmol) in dioxane (10 mL), stir the resulting mixture under nitrogen atmosphere at 100C for 16 hrs. Cool the reaction mixture to room temperature, filter off the solid, concentrate the filtrate under reduced pressure, purify by flash chromatography (silica gel, EtOAc:PE=2:l) to yield the title compound (296 mg, 92%). MS: (M+l): 323. |
92% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,4-dioxane; at 100.0℃; for 16.0h;Inert atmosphere; | Add benzophenone imine (215 mg, 1.19 mmol), cesium carbonate (640 mg, 1.96 mmol), (+-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (BINAP, 98 mg, 0.16 mmol), tris(dibenzylideneacetone)dipalladium [Pd2(dba)3, 90 mg, 0.098 mmol] to the solution of <strong>[1108724-32-8]3-bromo-5-(1,1-difluoroethyl)pyridine</strong> (200 mg, 0.9 mmol) in dioxane (10 mL), stir the resulting mixture under nitrogen atmosphere at 100 C. for 16 hrs. Cool the reaction mixture to room temperature, filter off the solid, concentrate the filtrate under reduced pressure, purify by flash chromatography (silica gel, EtOAc:PE=2:1) to yield the title compound (296 mg, 92%). MS: (M+1): 323. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With (bis-(2-methoxyethyl)amino)sulfur trufluoride; In dichloromethane; at 60.0℃;Sealed tube; | Heat the mixture of l-(5-bromopyridin-3-yl)ethanone (500 mg, 2.5 mmol), bis-(2-methoxyethyl)aminosulfur trifluoride (BAST, 2.2 g, 10 mmol) in dichloromethane (8 mL) in a sealed tube at 60C overnight. TLC (PE:EtOAc=l :l) shows the reaction is complete. Concentrate the mixture, purify the residue by flash chromatography (silica gel, PE:EtOAc=l :1) to afford the title compound (200 mg, 36%). MS: (M+1): 222/224. |
36% | With (bis-(2-methoxyethyl)amino)sulfur trufluoride; In dichloromethane; at 60.0℃;Sealed tube; | Heat the mixture of 1-(5-bromopyridin-3-yl)ethanone (500 mg, 2.5 mmol), bis-(2-methoxyethyl)aminosulfur trifluoride (BAST, 2.2 g, 10 mmol) in dichloromethane (8 mL) in a sealed tube at 60 C. overnight. TLC (PE:EtOAc=1:1) shows the reaction is complete. Concentrate the mixture, purify the residue by flash chromatography (silica gel, PE:EtOAc=1:1) to afford the title compound (200 mg, 36%). MS: (M+1): 222/224. |
With diethylamino-sulfur trifluoride; In dichloromethane; at 50.0℃; for 18.0h; | Step 1. 3-Bromo-5-(l,l-difluoroethyl)pyridine To a stirred solution of l-(5-bromopyridin-3-yl)ethanone (2.4 g, 12 mmol) in 24 mL of CH2CI2 was added DAST (15.5 mL, 96 mmol) dropwise over a period of 10 min. The mixture was heated to 50 C for 18 h. The mixture was cooled to RT and carefully poured into ice-cold 2N NaOH. The layers were separated and the aqueous phase was extracted with CH2CI2. The organic phases were combined, dried over a2S04, and the solvent was removed in vacuo. The crude product was chromatographed on an 80g S1O2 column using 0-30% EtOAc:hexane over 30 min at 60 mL/min. Fractions containing product were combined and the solvents were removed in vacuo to give the title compound. LCMS m/z (M+H)+ = 223.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; In toluene; at 100.0℃; for 1.5h;Inert atmosphere; | To a stirred solution of 3-bromo-5-(l, l-difluoroethyl)pyridine (1.86 g, 8.38 mmol) in 40 mL toluene was added vinyl tri-n-butylstannane (3.2 mL, 11 mmol) and the solution was sparged with nitrogen gas. Bis(triphenylphosphine)palladium(II) chloride (0.6 g, 0.8 mmol) was added and the mixture was heated to 100 C for 1.5 h. The mixture was cooled to RT, diluted with EtOAc, and washed with water and brine, then dried (MgS04), filtered and the solvent was removed in vacuo. The crude product was chromatographed on a 40 g S1O2 column using 0-40% EtOAc:hexane over 20 min at 40 mL/min. Fractions containing product were combined and the solvents were removed in vacuo to give the title compound. LCMS m/z = 170.1 (M+H)+. |
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