Structure of 101-70-2
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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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Deem, Madeleine C. ; Hein, Jason E. ;
Abstract: Online HPLC reaction progress monitoring provides detailed data-rich profiles; however, extracting kinetic information requires UV-visible response factors to determine concentrations from peak areas. If the reaction's overall mass balance is known and some anal. trend for all relevant species can be recorded, it is possible to estimate the absolute response factors of all species using a system of linear equations. We delineate a method using the Microsoft Solver plug-in to convert time course profiles to reagent concentrations without anal. standards
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Purchased from AmBeed: 207739-72-8 ; 128055-74-3 ; 101-70-2 ; 28320-32-3 ; 501-65-5 ; 103-30-0 ; 1754-62-7 ; 17619-97-5
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Application of time course-based kinetic methods to complex catalytic systems
Madeleine Deem ;
Abstract: Understanding and optimizing chemical reactions is important for controlling reaction selectivity, increasing yield, reducing waste, and improving numerous other reaction parameters. Reaction optimization is often informed by mechanistic understanding, which arises from kinetic studies. Kinetic studies aim to understand what impacts the mechanism and rate of a reaction. There are many methodologies for kinetic analysis. There have been recent advances in kinetic methodologies which allow for the interrogation of systems under reaction-relevant conditions, and which require fewer experiments than traditional initial rate methods. These modern kinetic methodologies utilize temporal profiles of chemical reactions that track the course of individual reaction components over the course of a reaction. Time course reaction profiles provide invaluable reaction insight and, coupled with these new kinetic methodologies, are extremely powerful tools for mechanistic elucidation. However, chemists have been slow to onboard these powerful methodologies, which are still considered advanced and niche techniques. This thesis aims to develop protocols to make these methodologies more accessible to the general chemistry community. A set of best practices for collecting robust and high-quality time course reaction profiles for kinetic studies was developed. This guide improves the confidence chemists have in the conclusions of kinetic studies by ensuring that important control reactions have been run and proper optimization of reaction monitoring parameters has been achieved. A protocol for converting data sets of temporal peak area versus time to temporal concentration using nonlinear regression analysis was also developed. This method is rapid, facile, and broadly accessible as it can be done with any nonlinear regression tool, including the Solver plug-in in Microsoft Excel. Lastly, the presented protocols and procedures were applied to gather kinetic data in the Buchwald Hartwig amination of a polyhalogenated arene. Time course data of the amination were gathered with several commonly employed catalyst systems. The time course profiles in combination with reaction modeling enabled delineation of two previously indistinguishable mechanisms, ring walking and diffusion controlled coupling. The resulting mechanistic understanding was leveraged to achieve a specific site selectivity in the amination of the polyhalogenated arene and enabled desymmetrization of the symmetrical starting material.
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CAS No. : | 101-70-2 |
Formula : | C14H15NO2 |
M.W : | 229.27 |
SMILES Code : | COC1=CC=C(NC2=CC=C(OC)C=C2)C=C1 |
MDL No. : | MFCD00014895 |
InChI Key : | VCOONNWIINSFBA-UHFFFAOYSA-N |
Pubchem ID : | 7571 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 68.97 |
TPSA ? Topological Polar Surface Area: Calculated from |
30.49 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.81 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.58 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.45 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.6 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.75 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.04 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.78 |
Solubility | 0.0385 mg/ml ; 0.000168 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.91 |
Solubility | 0.0284 mg/ml ; 0.000124 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.23 |
Solubility | 0.00135 mg/ml ; 0.0000059 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
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) |
Yes |
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 |
-5.16 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 |
0.0 |
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) |
1.79 |
* 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 |
---|---|---|
45% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate In toluene at 110℃; for 12 h; Inert atmosphere | Nitrogen gas in 50 mL 2-necked flask, the 4,4'-dimethoxydiphenylamine (2.00 g, 8.72 mmol), 2,2',7,7'-tetrabromo-9,9'-spirobi[9H-fluorene] (1.23 g, 1.94 mmol), sodium tertbutoxide (1.12 g, 11.6 mmol), tris (dibenzylideneacetone) dipalladium (0) (0.071 g, 0.078 mmol) and tri-tert-butylphosphine (0.025 g, 0.12 mmol) to put this in dry toluene 15mL was added to 110 °C and stirred for 12 hours. The reaction mixture was cooled to room temperature and extracted with ethyl acetate and dried with washed with brine MgSO4 The solvent was removed by separation and purification by column chromatography (ethyl acetate / hexane = 1/2) of the solid of the title compound as a beige It was obtained (45percent, 1.07 g) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40.2% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 80℃; for 8h; | To a 250 ml three-mouth bottle adding 5.04g (0.022 muM) precursor 1 (through the implementation of example one preparation) and 3.26g (0.01 muM) 2, 8 - dibromodiphenyl benzofuran, the mixture thus obtained is VI, VI is added to the mixture in the 40g toluene. Opening stirring, system for the picture and the turbid, N2Replacement system 10min. In the system by adding 2.8g (0.025 muM) tert-butanolate, 0.18g (2 × 10-4Mol) Pd2(Dba)3And 0.12g (4 × 10-4Mol) tri-butyl phosphine four fluoroborates, 80 °C reaction 8 hours. The said technological, cooling to 20 - 25 °C, the reaction liquid filtration, filtrate directly filtering of the silica gel column, eluting with toluene, the solvent under reduced pressure, to be brownish red color oil of 6.5g. In the above-mentioned crude product in adding toluene and hexane recrystallization (mass ratio of 2:1), vacuum drying oven drying 3h, gain the light yellow powder 2.5g, yield: 40.2percent. |
Tags: 101-70-2 synthesis path| 101-70-2 SDS| 101-70-2 COA| 101-70-2 purity| 101-70-2 application| 101-70-2 NMR| 101-70-2 COA| 101-70-2 structure
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