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Structure of 6346-09-4
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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.
4.5
*For Research Use Only !
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Qiao Lin ; Ethan H. Spielvogel ; Tianning Diao ;
Abstract: The capture of carbon-centered radicals at a nickel(II) center is commonly featured in recent cross-coupling and metallaphotoredox catalytic reactions. Despite its widespread application in catalysis, this fundamental step lacks experimental characterization. This report portrays radical capture at catalytically relevant nickel(II) centers from several aspects, including the structure-activity relationships of the ligands, the mechanism, the kinetics, and the stereoselectivity. Spectroscopic data provide evidence for the formation of a nickel(III) intermediate. Strikingly different reactivity between nickel-aryl and nickel-alkyl complexes implies different rate-determining steps for C(sp3)–C(sp3) and C(sp2)–C(sp3) bond formation. Kinetic data benchmark the capture rates on the scale of 10[7] M−1s−1 and 10[6] M−1s−1 for primary and secondary radicals, respectively. Overall, the activation energy is higher than that of previous computational estimations. Finally, stoichiometric experiments with well-defined chiral nickel complexes demonstrate that the radical trapping step can confer diastereoselectivity and enantioselectivity with a drastic ligand effect.
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Purchased from AmBeed: 142946-79-0 ; 50487-71-3 ; 3395-91-3 ; 22980-76-3 ; 2706576-80-7 ; 119165-69-4 ; 402-43-7 ; 27060-75-9 ; 6346-09-4 ; 117408-98-7 ; 957034-45-6 ; 7318-00-5 ; 403-39-4 ; 366-18-7 ; 401-79-6 ; 929000-62-4 ; 459-47-2 ; 1416819-91-4 ; 605-39-0 ; 44565-27-7 ; 10285-80-0 ; 458-76-4 ; 5789-35-5 ; 1165-06-6 ; 1595706-68-5 ; 27820-98-0
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CAS No. : | 6346-09-4 |
Formula : | C8H19NO2 |
M.W : | 161.24 |
SMILES Code : | NCCCC(OCC)OCC |
MDL No. : | MFCD00008227 |
InChI Key : | GFLPSABXBDCMCN-UHFFFAOYSA-N |
Pubchem ID : | 80672 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314-H227 |
Precautionary Statements: | P501-P210-P264-P280-P370+P378-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338+P310-P403+P235-P405 |
Class: | 8 |
UN#: | 2735 |
Packing Group: | Ⅲ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 45.45 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.48 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.4 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.6 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.12 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.82 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.98 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.18 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.76 |
Solubility | 28.3 mg/ml ; 0.176 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.11 |
Solubility | 12.6 mg/ml ; 0.078 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.84 |
Solubility | 2.34 mg/ml ; 0.0145 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) |
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 |
-6.86 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 |
1.0 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) |
2.2 |
* 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 |
---|---|---|
The compound (1.04 g) obtained in Example 23-3 was dissolved in anhydrous methanol (40 ml) and added with 4,4-diethoxy-butylamine (863 mg) and trimethyl orthoformate (1.44 ml). The whole was stirred at room temperature for 3 hours. The solution was added with sodium borohydride (499 mg) and the whole was stirred at room temperature for 30 minutes. After completion of the reaction, the solvent was distilled off. The resultant was added with water, subjected to extraction with chloroform, and then dried with magnesium sulfate. The solvent was distilled off. The residue was purified through silica gel column chromatography (hexane/ethyl acetate). The resultant was dissolved in methanol (25 ml) and water (4.8 ml) and added with acrylonitrile (0.43 ml). The whole was stirred at room temperature for 16.5 hours. After completion of the reaction, the solvent was distilled off. The resultant was subjected to extraction with chloroform and dried with magnesium sulfate. The solvent was distilled off. The resultant was dissolved in THF (12 ml), acetone (12 ml), and 1 mol/l hydrochloric acid (12 ml) and the whole was stirred at room temperature for 3 hours. After completion of the reaction, the solvent was distilled off. The resultant was added with a 1 mol/l sodium hydroxide aqueous solution and the whole was subjected to extraction with chloroform. The resultant was dried with magnesium sulfate and the solvent was distilled off. The resultant was dissolved in anhydrous methanol (26 ml) and added with piperidine (0.49 ml) and sodium cyanoborohydride (415 mg). After the solution was adjusted to pH 5 with acetic acid, the whole was stirred at room temperature for 3 days. After completion of the reaction, the solvent was distilled off. The resultant was added with a 1 mol/l sodium hydroxide aqueous solution and the whole was subj ected to extraction with chloroform. The resultant was dried with magnesium sulfate and the solvent was distilled off. The residue was purified through silica gel column chromatography (hexane/ethyl acetate), thereby obtaining the subject compound (1.13 g) as a colorless oily substance. MS(FAB,Pos.):m/z=429[M+H]+ 1H-NMR(500MHz,CDCl3):delta=1.27-1.50(6H,m),1.47(9H,s),1.55-1.60(4H,m),2.25(2H,t,J=7.3Hz),2.34(4H,br),2.40(2H,t,J=7.0Hz),2.49(2H,t,J=6.9Hz),2.77(2H,t,J=7.0Hz),3.59(2H,s),4.31(2H,d,J=5.5Hz),7.23(2H,d,J=7.9Hz),7.29(2H,d,J=8.2Hz). |
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