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Structure of 589-16-2
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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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Photosensitized activation of diazonium derivatives for C-B bond formation
Ripak, Alexia ; De Kreijger, Simon ; Sampaio, Renato N. ; Vincent, Cooper A. ; Cauet, Emilie ; Jabin, Ivan , et al.
Abstract: Aryl diazonium salts are ubiquitous building blocks in chem., as they are useful radical precursors in organic synthesis as well as for the functionalization of solid materials. They can be reduced electrochem. or through a photo-induced electron transfer reaction. Here, we provide a detailed picture of the ground- and excited-state reactivity of a series of nine rare and earth-abundant photosensitizers with 13 aryl diazonium salts, which also included three macrocyclic calix[4]arene tetradiazonium salts. Nanosecond transient absorption spectroscopy confirmed the occurrence of excited-state electron transfer and was used to quantify cage-escape yields (i.e., the efficiency with which the formed radicals sep. and escape the solvent cage). Cage-escape yields were large; they increased when the driving force for photo-induced electron transfer increased and also tracked with the C-N+2 bond cleavage propensity, among others. A photo-induced borylation reaction was then investigated with all the photosensitizers and proceeded with yields between 9% and 74%.
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CAS No. : | 589-16-2 |
Formula : | C8H11N |
M.W : | 121.18 |
SMILES Code : | NC1=CC=C(CC)C=C1 |
MDL No. : | MFCD00007921 |
InChI Key : | HRXZRAXKKNUKRF-UHFFFAOYSA-N |
Pubchem ID : | 11504 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H227-H301+H311+H331-H373-H402 |
Precautionary Statements: | P210-P260-P264-P270-P271-P273-P280-P301+P310+P330-P302+P352+P312-P304+P340+P311-P314-P370+P378-P403+P233-P403+P235-P405-P501 |
Class: | 6.1 |
UN#: | 2810 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.62 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.69 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.96 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.84 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.14 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.92 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.25 |
Solubility | 0.676 mg/ml ; 0.00558 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.13 |
Solubility | 0.895 mg/ml ; 0.00739 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.78 |
Solubility | 0.2 mg/ml ; 0.00165 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) |
Yes |
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 |
-5.65 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 |
1.0 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) |
1.0 |
* 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 |
---|---|---|
A solution of pyridine (3.46 ml, 43 [MMOL),] 4-ethyl aniline (0.69 ml, 5.37 [MMOL)] and phosgene (11.1 [ML,] 20 % in toluene ; 21.5 [MMOL)] in CH2CI2 (66 mL) is stirred at 0 [C] overnight. After concentrating under reduced pressure, the reaction mixture is taken in THF (26 [ML),] filtrated, and added to a solution of 4- (pyridin-4-yl-oxy)-phenylamine (Stage 1.1 ; 0.5 g, 2.69 [MMOL)] and pyridine (0.43 ml, 0.43 [MMOL)] in THF (3.3 ml) and stirred at rt for 24 h. The reaction solution is filtered over silica gel (30 g), taken up in AcOEt (100 ml), washed with [H2O] (20 [ML),] [NAHC03] (5 %, 20 [ML),] and brine (20 [ML,] 2x), dried over [NA2SO4,] concentrated under reduced pressure, and flash chromatographed (silica gel, [2 X 18] cm; AcOEt/hexane = 2: [1 #] 4: 1) giving compound of Example 1 as a colorless solid; M+H = 334, 1H-NMR (400 MHz, DMSO-d6) : 8. 70 (s, 1 H, NH), 8.60 (s, 1 H, NH), 8.44 (d, Hz, 6.5 Hz, 2H, pyridinyl), 7.54 (d, 9.5 Hz, 2H, [4-ETHYL-PHENYL),] 7.37 (d, 9.5 Hz, 2H, oxo-phenyl-amine), 7.11 (d/d, 9.5 Hz, 4H, oxo- [PHENYL-AMINEL 4-ETHYL-PHENYL), 6.] 89 (d, 6.5 Hz, [2H,] [PYRIDINYL),] 2.55 (qu, 7.5 Hz, 2H, [CH2),] 1.16 (t, 7.5 hz, 3H, CH3) ; Rf [(ACOET/HEXANE] = 2: 1): 0.16 ; m. p. = 166.5-168 [C.] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With polyvinyl pyridine (PVP); In ethanol; at 20℃; for 18h; | General procedure: Arylamine (1 mmol), alkylisothiocyanate (1 mmol) and 2-bromo-2-(2-fluoro-phenyl)-1-cyclopropylethanone (1 mmol) were added simultaneously to a round-bottomed flask containing EtOH (10 mL). Polyvinyl pyridine (0.2 mmol) was added in one portion to the mixture. The mixture was stirred at room temperature for the appropriate time (Table 1). The progress of the reaction was monitored by thin-layer chromatography (TLC). After the completion of the reaction, the solid residue was filtered and then recrystallized from EtOH=H2O (1:1v=v) to yield pure products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With polyvinyl pyridine (PVP); In ethanol; at 20℃; for 14h; | General procedure: Arylamine (1 mmol), alkylisothiocyanate (1 mmol) and 2-bromo-2-(2-fluoro-phenyl)-1-cyclopropylethanone (1 mmol) were added simultaneously to a round-bottomed flask containing EtOH (10 mL). Polyvinyl pyridine (0.2 mmol) was added in one portion to the mixture. The mixture was stirred at room temperature for the appropriate time (Table 1). The progress of the reaction was monitored by thin-layer chromatography (TLC). After the completion of the reaction, the solid residue was filtered and then recrystallized from EtOH=H2O (1:1v=v) to yield pure products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 60℃; | General procedure: A solution of <strong>[848398-41-4]2,4-dichloro-5,7-dihydrofuro[3,4-d]pyrimidine</strong> (4, 1.89g, 10mmol) in DMSO (10mL) was added commercially available 3,4-dimethoxyaniline (1.53g, 10mmol) and DIPEA (2.58g, 20mmol). The solution was heated to 60C and stirred overnight. Then the solution was poured into water and extracted with EtOAc, the organic layer was washed by brine, dried with anhydrous Na2SO4, and filtered and concentrated under reduced pressure. The crude product was further purified by flash chromatography on silica gel (EtOAc/hexane=1:1) to afford 8 compound 5 (2.00g, yield 65%) as an off-white solid. 1H NMR (400MHz, CDCl3) delta: 6.90-6.81 (m, 3H), 4.88 (s, 2H), 4.42 (s, 2H), 3.92 (s, 3H), 3.89 (s, 3H). |
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