Structure of 67665-47-8
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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. : | 67665-47-8 |
Formula : | C25H14Br2 |
M.W : | 474.19 |
SMILES Code : | BrC1=CC(C23C4=C(C5=C2C=CC=C5)C=CC(Br)=C4)=C(C6=C3C=CC=C6)C=C1 |
MDL No. : | MFCD08704219 |
InChI Key : | OZZSXAWYZYTWQD-UHFFFAOYSA-N |
Pubchem ID : | 11282885 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 27 |
Num. arom. heavy atoms | 24 |
Fraction Csp3 | 0.04 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 118.14 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
4.22 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
7.76 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
7.56 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
7.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
7.89 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
6.93 |
Log S (ESOL):? ESOL: Topological method implemented from |
-8.33 |
Solubility | 0.00000224 mg/ml ; 0.0000000047 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-7.6 |
Solubility | 0.0000118 mg/ml ; 0.0000000249 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-11.76 |
Solubility | 0.0000000008 mg/ml ; 0.0 mol/l |
Class? Solubility class: Log S scale |
Insoluble |
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) |
Yes |
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) |
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 |
-3.68 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 |
1.0 |
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 |
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) |
3.75 |
* 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 |
---|---|---|
73.2% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 105 - 110℃; for 5h;Inert atmosphere; | 250mL Three-necked flask was added 1.04g (2.2 × 10-3mol) 2,2'- dibromo spirofluorene, 3.21g (4.4 × 10-3mol) intermediate 9 (prepared by Example a), 0.64g (6.6 × 10 -3mol) sodium tert-butoxide and 50.0g of toluene, was added 0.06g (6.6 × 10-5mol) under nitrogen Pd2 (dba) 3,0.025g (1.32 × 10-4mol) (t-Bu) 3PH · BF4, heating to 105 ~ 110 reaction 5h. The reaction was completed, the reaction solution was filtered, and the filtrate washed with water 50g × 2. The organic phase was dried over anhydrous sodium sulfate, and columned on silica gel, toluene off under reduced pressure. Recrystallized from ethanol to give pale yellow powdery solid 2.86g, yield 73.2percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27.6% | With 1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 70℃; for 18h;Inert atmosphere; | Compound A (2.00 g, 4.22 mmol), bis (pinacolato) diboron (2.36 g, 9.30 mmol), [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (II) ([1,1'-Bis (diphenylphosphino) ferrocene] dichloropalladium (II), Pd (dppf) Cl2) (0.31g, 0.42mmol), 1,1'-bis (diphenylphosphino) ferrocene (1 Flask of 70 mL of 1'-bis (diphenylphosphino) ferrocene, dppf) (0.234 g, 0.42 mmol), potassium acetate (KOAc) (2.55 g, 26 mmol) and 1,4-dioxane (1,4-dioxaen) Was charged with nitrogen and reacted at 70 C. for 18 hours. After cooling to room temperature, the product was extracted with methylene chloride (MC) and washed well with water. The extracted organics were dried over anhydrous magnesium sulfate (anhydrous MgSO 4). Then, the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 20: 1 (eluent)) to obtain 1.58 g of compound A-1. (Yield 27.6%) GC-MS: 568.22 is a diagram showing an MS measurement result of Compound A-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.2% | With tri-tert-butyl phosphine; potassium tert-butylate; palladium diacetate; In toluene; at 100℃; for 20h;Inert atmosphere; Schlenk technique; | 100 mL with argon substitution, equipped with a stirrerTo a Schlenk tube of N-phenyldibenzo [b, d] furan-4-amine (1.15 g, 4.43 mmol), <strong>[67665-47-8]2,2'-dibromo-9,9'-spirobifluorene</strong> (1.00 g, 11 mmol), palladium acetate (40 mg, 0.18 mmol), toluene (40 mL)Tri-t-butylphosphine (36 mg, 0.18 mmol) and potassium t-butoxide (1.0 g, 8.9 mmol) were placed and sealed, followed by stirring at 100 ° C. for 20 hours.Thereafter, the reaction vessel was allowed to cool to near room temperature, the lid was opened, and water (30 mL) was added thereto. The content was transferred to a separating funnel, the organic layer and the aqueous layer were separated, the aqueous layer was removed, and the organic layer was washed with water.The organic layer was dried over sodium sulfate. Thereafter, sodium sulfate was removed by filtration, and the organic layer was concentrated.The concentrated mixture was purified by silica gel column chromatography (developing solvent: hexane / dichloromethane = 3/1) to obtain the objective compound represented by the above chemical formula (31) (yield 1.51 g, yield Rate 86.2percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With tri-tert-butyl phosphine; potassium tert-butylate; palladium diacetate; In toluene; at 100℃; for 20h;Schlenk technique; Inert atmosphere; Sealed tube; | A stirrer,N-phenyldibenzo [b, d] thiophene-4-amine (0.55 g, 2.0 mmol) was added to a 100 mL Schlenk flask purged with argon,<strong>[67665-47-8]2,2'-dibromo-9,9'-spirobifluorene</strong> (0.47 g, 1.0 mmol),Palladium acetate (9.0 mg, 0.04 mmol),Toluene (40 mL), tri-t-butylphosphine (8.1 mg,0.04 mmol) and potassium t-butoxide (0.22 g, 2.0 mmol) were put in a reaction vessel and sealed,And the mixture was stirred at 100 ° C. for 20 hours. Thereafter, the reaction vessel was allowed to cool to near room temperature,Open the lid and put water (30 mL) into it. Transfer contents to a separating funnel,After separating the organic phase and aqueous phase, the aqueous phase was removed and the organic phase was washed with water.The organic phase was dried over sodium sulfate. after that,The sodium sulfate was removed by filtration and the organic phase was concentrated.The concentrated mixture was purified by silica gel column chromatography (developing solvent: hexane / dichloromethane = 3/1)To obtain a target compound represented by the above general formula (6)(Yield 0.38 g, yield 44.0percent). |