Structure of 105946-82-5
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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. : | 105946-82-5 |
Formula : | C12H8BrI |
M.W : | 359.00 |
SMILES Code : | IC1=CC=C(C2=CC=C(Br)C=C2)C=C1 |
MDL No. : | MFCD17676204 |
InChI Key : | GWOAJJWBCSUGHH-UHFFFAOYSA-N |
Pubchem ID : | 10904452 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 72.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.61 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.72 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.16 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.77 |
Log S (ESOL):? ESOL: Topological method implemented from |
-6.17 |
Solubility | 0.000244 mg/ml ; 0.000000679 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.37 |
Solubility | 0.00152 mg/ml ; 0.00000424 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.67 |
Solubility | 0.0000768 mg/ml ; 0.000000214 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
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 |
-4.51 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 |
2.0 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.15 |
* 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 |
---|---|---|
62% | With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In toluene; at 90℃; for 3h; | Synthesis Example 6: Synthesis of Intermediate 6 16.2 g (45 mmol) of 4-bromo-4'-iodo-biphenyl, 6.58 g (30 mmol) of N-phenyl-2-naphthylamine, 4.3 g (45 mmol) of t-BuONa, 0.55 g (0.6 mmol) of Pd2(dba)3, and 0.12 g (0.6 mmol) of P(t-Bu)3 were dissolved in 100 mL of toluene and stirred at 90C for 3 hours. After the reaction was completed, the reaction product was cooled to room temperature and extracted three times with distilled water and 100 ml of diethylether. An organic layer was collected and dried using magnesium sulfate to evaporate the solvent. The residue was separated and purified using silica gel column chromatography to obtain 8.38 g (yield: 62%) of Intermediate 6. This compound was identified using HR-MS. C28H20BrN calc.: 449.0779; and found: 449.0775. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With copper; potassium carbonate; sodium sulfate; In nitrobenzene; | The starting material, N-phenylnaphthalen-1-amine (65.8g, 300mmol) in 4-bromo-4'-iodo-1,1'-biphenyl (129.2g, 360mmol), Na2SO4 (42.6g, 300mmol), K2CO3 (41.4 g, 300mmol), Cu (5.72g, 90mmol), to the use of the nitrobenzene product synthesis example 89.2g (yield 66% was obtained). |
66% | With copper; potassium carbonate; sodium sulfate; In nitrobenzene; at 200℃; | Starting material, N-phenylnaphthalen-1-amine (65.8 g, 300 mmol), 4-bromo-4'-iodo-1,1'-biphenyl (129.2 g, 360mmol), Na2SO4 (42.6 g, 300 mmol), K2CO3 (41.4 g, 300 mmol), Cu (5.72 g, 90 mmol), nitrobenzene was obtained using the synthesis method of Sub 1-1 of Example 2 above to obtain 89.2 g of product (yield: 66%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 4h; | P2 (60 g, 1 eq), 4-bromo-4'-iodo-1,1'-biphenyl (4-bromo-4'-iodo-1,1'-biphenyl) (63 g, 1.3 eq) Pd (PPh3) 4 (7.8 g, 0.05 eq), K2CO3 (28 g, 1.5 eq), toluene (toluene) 600 ml, ethanol (Ethanol) 100 ml, H2O 100ml Is placed in a round bottom flask (1-neck-R.B.F.) and stirred. (4h) MC hot filter was performed twice to obtain intermediate (1). (33 g, Step yield = 54%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper nitrate hemi(pentahydrate); 4,4'-bis(carbomethoxy)-2,2'-bipyridine; sodium amide; In N,N-dimethyl-formamide; at 130℃; for 15h; | General procedure: Under air atmosphere, a reaction tube was charged with aryl iodides (0.5 mmol), Ph3P+CF2CO2- (268 mg, 0.75 mmol, 1.5equiv), L4 (6.3 mg, 5 mol %), Cu (NO3)2·2.5H2O (143 mg, 0.65 mmol, 1.3 equiv), NaNH2 (39 mg, 1.0 mmol, 2.0 equiv) and dry DMF (4 mL). The resulting mixture was stirred at 130C for 15 h. After being cooled to room temperature, the mixture was filtered through a pad of Celite. The solid was washed with DCM, and the combined organic phase was washed with water (15 mL × 3). The organic layer was further washed with saturated sodium sulfite and saturated brine, and then dried with sodium sulfate. After the solvent was removed by concentration under vacuum, the residue was subjected to flash column chromatography to afford the final product. |