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Structure of DPPF
CAS No.: 12150-46-8
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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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Palladium-catalyzed dearomative 1, 4-hydroamination
Gilbert, Robert ; Davis, Christopher W ; Bingham, Tanner W ; Sarlah, David ;
Abstract: A dearomative 1,4-hydroamination of nonactivated arenes has been developed, using a key arene-arenophile photocycloaddition strategy to disrupt aromaticity. Palladium catalysis with K-Selectride® as a hydride source uniquely enables selective reactivity and provides access to a range of substituted 1,4-cyclohexadienes from aromatic starting materials. We demonstrate a few synthetic applications of this scalable procedure by preparing highly-functionalized small molecules in three to four steps from naphthalene.
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Keywords: Dearomatization ; Hydroamination ; Arenophiles ; Palladium ; Catalysis
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Purchased from AmBeed: 32005-36-0 ; 657408-07-6 ; 787618-22-8 ; 213697-53-1 ; 12150-46-8
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CAS No. : | 12150-46-8 |
Formula : | C34H28FeP2 |
M.W : | 554.38 |
SMILES Code : | C1(P([C-]23[CH]4=[CH]5[CH]6=[CH]2[Fe+2]5643789%10[CH]%11=[CH]7[C-]8(P(C%12=CC=CC=C%12)C%13=CC=CC=C%13)[CH]9=[CH]%11%10)C%14=CC=CC=C%14)=CC=CC=C1 |
MDL No. : | MFCD00001422 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P310-P302+P352-P304+P340-P312-P330-P363-P405-P501 |
Class: | 6.1 |
UN#: | 3467 |
Packing Group: | Ⅲ |
Num. heavy atoms | 37 |
Num. arom. heavy atoms | 24 |
Fraction Csp3 | 0.06 |
Num. rotatable bonds | 8 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 160.09 |
TPSA ? Topological Polar Surface Area: Calculated from |
27.18 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
7.92 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
7.82 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
7.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
7.39 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
6.14 |
Log S (ESOL):? ESOL: Topological method implemented from |
-8.22 |
Solubility | 0.00000335 mg/ml ; 0.000000006 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-8.34 |
Solubility | 0.00000253 mg/ml ; 0.0000000046 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-11.0 |
Solubility | 0.0000000056 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) |
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) |
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 |
-4.06 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
2.0 |
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 |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.17 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<3.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
6.56 |
* 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 |
---|---|---|
In acetonitrile; for 4h;Heating / reflux; | Palladium diammine dichloride and 1 mole equivalent of 1 ,2bis(diphenylphosphino)ferrocene (dppf) were suspended in acetonitrile at reflux for 4 hrs. A basic gas (believed to be ammonia) was evolved during the reaction. The product was filtered off at room temperature and dried. The product contained 7.29percent Fe and 14.44percent Pd by standard wet chemical analysis and was identified as Pd(dppf)CI2 by infra-red spectroscopy. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | In dichloromethane; for 8h;Inert atmosphere; Schlenk technique; Reflux; | To a dichloromethane solution (15 cm3) of dppf (189 mg, 0.34 mmol), a methanolic solution of Na2PdCl4 (100 mg, 0.34 mmol) was added with continuous stirring. The resulting reaction mixture was refluxed for 8 hours. The solvents were evaporated in vacuo and the residue was washed thoroughly with diethyl ether to remove excess phosphine. The residue was extracted with dichloromethane, filtered and passed through a Florisil column. The resulting solution on refrigeration at ?5 oC afforded reddish orange crystals.(yield 214 mg, 86percent). Anal. Calcd. for C34H28P2FePdCl2 : C, 55.81 ; H, 3.86 percent. Found: C, 55.86; H, 3.85 percent. 1H NMR (CDCl3) delta: 4.26 (br, 4H, C5H4), 4.71 (br, 4H, C5H4), 7.41-7.49 (m, Ph), 7.56-7.82 (m, Ph); 31P{1H}NMR (CDCl3) delta : 34.1 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogenchloride; In ethanol; for 3h;Reflux; | The solution of dppf (1.6632g, 3mmol)in 15ml CH2Cl2 was added to a solution of PdCl2(0.5320g, 3mmol) that dissolved in 2 cm3 ethanoland 2 cm3 concentrate HCl. The mixture was reuxfor 3 hrs. And then the solvent was evaporate at roomtemperature to give red precipitate. A small portion ofthis complex was dissolve in CH2Cl2 and set to slowevaporation at room temperature after a few days, thered colored needle crystals were formed suitable forsingle-crystal diffraction analysis15. The melting pointis 253°C, yield is 2.086gm (95percent), formula: [Pd(k2-dppf)Cl2] and M.wt.is 816.58 gm/mole, as shown inFigure 1. |