Structure of 447-53-0
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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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Highly selective catalytic transfer hydrodeuteration of cyclic alkenes
Hintzsche, Samuel J. ; Vang, Zoua Pa ; Rivera Torres, Emanuel ; Podoski, Mykaela ; Clark, Joseph R. ;
Abstract: Selective deuterium installation into small molecules is becoming increasingly desirable not only for the elucidation of mechanistic pathways and studying biological processes but also because of deuterium's ability to favorably adjust the pharmacokinetic parameters of bioactive molecules. Fused bicyclic moieties, especially those containing heteroatoms, are prevalent in drug discovery and pharmaceuticals. Herein, we report a copper-catalyzed transfer hydrodeuteration of cyclic and heterocyclic alkenes, which enables the synthesis of chromans, quinolinones, and tetrahydronaphthalenes that are precisely deuterated at the benzylic position. We also demonstrate the ability to place one deuterium atom at the homobenzylic site of these scaffolds with high regioselectivity by swapping transfer reagents for their isotopic analogs. Furthermore, examples of chemoselective transfer hydrogenation and transfer deuteration are disclosed, allowing for the simultaneous incorporation of two vicinal hydrogen or deuterium atoms into a double bond.
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Keywords: copper ; deuteration ; hydrodeuteration ; hydrogenation ; transition metal catalysis
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Purchased from AmBeed: 6836-19-7 ; 14243-64-2 ; 19315-93-6 ; 1810-66-8 ; 584-08-7 ; 189114-61-2 ; 447-53-0
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CAS No. : | 447-53-0 |
Formula : | C10H10 |
M.W : | 130.19 |
SMILES Code : | C12=C(CCC=C2)C=CC=C1 |
MDL No. : | MFCD00001672 |
InChI Key : | KEIFWROAQVVDBN-UHFFFAOYSA-N |
Pubchem ID : | 9938 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.19 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.17 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.99 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.05 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.99 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.12 |
Solubility | 0.0988 mg/ml ; 0.000759 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.89 |
Solubility | 0.167 mg/ml ; 0.00128 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.0 |
Solubility | 0.13 mg/ml ; 0.001 mol/l |
Class? Solubility class: Log S scale |
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 |
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) |
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) |
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 |
-4.81 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 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.29 |
* 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 |
---|---|---|
10% | With palladium diacetate; silver carbonate; In acetone; at 70℃; for 4h; | General procedure: To a stirred solution of 6 (0.5 mmol), tosyl-2-iodoaniline 5a or 5e (0.75 mmol), mesyl-2-iodo-aniline 5b (0.75 mmol), Cbz-2-iodoaniline 5c (0.75 mmol) or Acetyl-2iodoaniline 5d (0.75 mmol), in acetone (5 mL), silver-carbonate (1.5 mmol) and Pd(OAc)2 (0.005 mmol) were added. The reaction mixture was refluxed for 4 h and filtered in celite with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated. The crude product was washed in n-hexane and purified by flash chromatography on silica. |