Structure of 603-34-9
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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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CAS No. : | 603-34-9 |
Formula : | C18H15N |
M.W : | 245.32 |
SMILES Code : | N(C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3 |
MDL No. : | MFCD00003020 |
InChI Key : | ODHXBMXNKOYIBV-UHFFFAOYSA-N |
Pubchem ID : | 11775 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 18 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 81.13 |
TPSA ? Topological Polar Surface Area: Calculated from |
3.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.19 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.74 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.16 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.9 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.76 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.55 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.48 |
Solubility | 0.000812 mg/ml ; 0.00000331 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.58 |
Solubility | 0.000652 mg/ml ; 0.00000266 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.77 |
Solubility | 0.0000414 mg/ml ; 0.000000169 mol/l |
Class? Solubility class: Log S scale |
Poorly 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 |
No |
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 |
-3.72 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.89 |
* 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 |
---|---|---|
99% | Synthesis Example 4Tris(4-iodophenyl)amine was prepared as follows. Firstly, a mixture of IPy2BF4 (5.3 g, 14.3 mmol) and triphenylamine (1 g, 4.1 mmol) was added with dist. CH2Cl2 (60 mL) under a nitrogen atmosphere, and then was added dropwise at 0 C. with trifluoromethanesulfonic acid (TfOH: 900 muL, 4.1 mmol). Thereafter, the resultant mixture was stirred under a nitrogen atmosphere at room temperature for 21 hours to obtain a reddish-brown reaction mixture. Subsequently, the obtained reaction mixture was added with sat. Na2S2O3, and an aqueous layer wad extracted with CH2Cl2. After that, an organic layer thus collected was washed with sat. NaCl, and dried with Na2SO4. Subsequently, the dried organic layer was filtered and concentrated to obtain a crude product. Then, the obtained crude product was separated and purified by silica gel column chromatography (hexane/EtOAc=5/1) to obtain tris(4-iodophenyl) amine (2.507 g, 99% yield).The obtained compound was subjected to 1H NMR and 13C NMR measurements. The obtained results are shown below.1H NMR (CDCl3) delta7.54 (d, J=8.9 Hz, 6H), 6.81 (d, J=8.9 Hz, 6H).13C NMR (CDCl3) delta146.5, 138.4, 126.0, 86.6.From the NMR measurement results, it was confirmed that the obtained compound was tris(4-iodophenyl)amine. | |
99% | A mixture of 5.3 g (14.3 mmol, 3.5 eq.) of bis(pyridine)iodonium tetrafluoroborate (IPy2BF4) and 1 g (4.1 mmol) of triphenylamine was added with 60 ml of dichloromethane (dist.CH2Cl2) under a nitrogen atmosphere to obtain a mixed solution. Then, the mixed solution thus obtained was cooled to 0 C., and added dropwise with 900 mul (4.1 mmol, 1 eq.) of trifluoromethanesulfonic acid (TfOH). The resultant mixed solution was stirred under a nitrogen atmosphere at room temperature for 21 hours to obtain a reaction mixture. Subsequently, the reaction mixture thus obtained was added with a saturated sodium thiosulfate (Na2S2O3) aqueous solution to suppress the reaction. Thereafter, the aqueous phase in the reaction solution was extracted with dichloromethane. Thereby, the organic phase containing the reddish-brown reaction mixture was obtained. After that, the organic phase thus obtained was washed with a saturated NaCl solution, dried with Na2SO4, filtered, and concentrated to obtain a crude product (2.9714 g). Then, the crude product thus obtained was separated and purified by silica gel column chromatography (hexane:ethyl acetate=5:1). Thereby, tris(4-iodophenyl)amine was obtained (a yield of 2.507 g and 99%).The tris(4-iodophenyl)amine thus obtained was subjected to 13C NMR and 1H NMR measurements. Note that, the NMR spectra were measured with a JOEL JNM EX270 spectrometer (270 MHz for 1H). Moreover, TMS was used as a reference for the chemical shifts in 1H NMR, and CDCl3 was used as a reference for the chemical shifts in 13C NMR. The measurement results are shown below.1H NMR (CDCl3) delta7.54 (d, J=8.9 Hz, 6H), 6.81 (d, J=8.9 Hz, 6H);13C NMR (CDCl3) delta146.5, 138.4, 126.0, 86.6.In addition, the following reaction formula (H) shows an outline of the synthesis method for the tris(4-iodophenyl)amine. | |
94.5% | With potassium iodate; acetic acid; potassium iodide; for 4h;Reflux; | In a 500 mL three-necked flask equipped with a spherical condenser and a stirrer, 4.90 g of triphenylamine was sequentially added.7.30 g of potassium iodide and 200 mL of acetic acid were heated to reflux, and then 6.40 g of potassium iodate was added to the reaction bottle in batches, and the reaction was performed at a constant temperature for 4 hours.The reaction solution changed from colorless to brown and finally colorless. Stop heating and cool to room temperature.Spin off the acetic acid, add saturated sodium thiosulfate solution and dichloromethane for extraction, and dry the organic phase over anhydrous sodium sulfate.Concentration gave 12.50 g of a pale yellow solid, which was recrystallized from ethyl acetate.11.77 g of light yellow platelets were obtained with a yield of 94.50%. |
90% | With iodine; mercury(II) oxide; In ethanol; at 20℃; | A mixture of triphenylamine (1 g, 0.004 mmol), HgO (4.06 g, 0.019 mmol) and I2 (5.08 g,0.020 mmol) in EtOH (50 mL) was stirred overnight at room temperature. The solvent was removed, and the product was separated from mercuric salts with boiling toluene. The solution was filtered through the short column of Al2O3, and the product was precipitated from hot toluene with MeOH to afford the title compound 4as white solid (2.33 g, 90%). Mp: 170C. 1H NMR (300 MHz, CDCl3)d(ppm): 7.53 (d, J8.8 Hz, 6H), 6.81 (d,J8.8 Hz, 6H); 13C NMR (75 MHz, CDCl3) d (ppm): 86.76, 126.12, 138.53, 146.59.23 |
90% | At room temperature, 24.5 g of triphenylamine, 300 mL of anhydrous ethanol, and 70 g of mercury oxide were added to the reaction system.Stir at room temperature for 1 h. Then 80 g of iodine was added and the reaction was maintained at room temperature for 12 h.The reaction mixture was distilled under reduced pressure and ethanol was recovered. 300 mL of benzene was added to the solid phase for recrystallization.A white crystalline product, tris-(4-iodophenyl)amine, was obtained, yield 56 g, yield 90%. | |
88% | With N-iodo-succinimide; acetic acid; In chloroform; | Tris(4-iodophenyl)amine (1). To a stirred mixture of triphenylamine (7.36 g, 30.0 mmol) and N-iodosuccinimide (NIS, 21.60 g, 96.0 mmol) in chloroform (180 mL) was added acetic acid (120 mL) at room temperature under exclusion of light. The solution was stirred overnight at room temperature. The reaction mixture was poured into water, washed with sodium thiosulfate, and extracted with methylene chloride. The combined methylene chloride layers were washed with water, dried with Na2SO4, and concentrated. The crude product was purified over a silica gel column with hexane/methylene chloride (7:1) as eluent to afford a slightly brown solid (16.54 g, 88%). 1H NMR (300 MHz, CDCl3): delta 7.56 (d, 6H, J=8.7 Hz), 6.83 (d, 6H, J=9.0 Hz). |
With potassium iodate; acetic acid; potassium iodide; at 120℃; for 4h; | Triarylamine(10 g, 40 mmol) was added to a three-necked flask, potassium iodide (14.36 g, 88.81 mmol), 150 ml of glacial acetic acid was added, and the reaction was refluxed at 120 C.Potassium iodate (9.52 g, 44.41 mmol) was added portionwise to the above reaction for 4 h.The treatment method after the end of the reaction is in agreement with the 2I-Cz treatment method.A pale yellow solid powder 3I-TPA was obtained with a yield of about 71%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In a 250 mL two-neck round bottom flask equipped with magnetic stirrer, condenser and nitrogen inlet-outlet were introduced triphenylamine (8 g, 3.2 mmol), KI (7.19 g, 4.3 mmol), and glacial acetic acid (120 mL). The mixture was stirred in nitrogen atmosphere at 85 °C for 5 h and KIO3 (4.60 g, 2.15 mmol) was introduced over 5 h. The mixture was precipitated in water and a dirty white compound was obtained and purified by column chromatography using ethyl acetate/hexane (1:5) as eluent. Yield: 66percent,Mp 69-70 C. 1H NMR (CDCl3, ppm): 7.50 (4H, d, J 8.8 Hz), 7.24(2H, d, J 8.0 Hz), 7.06-7.04 (3H, d t), 6.82-6.80 (4H, d,J 8.8 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; at 20℃;Inert atmosphere; | (5) Under the protection of argon, triphenylamine (25 g, 0.407 mol), triethylamine (30 mL), cuprous iodide(0.35 g, 0.00203 mol), followed by the dropwise addition of trimethylsilylacetylene (34.5 ml, 0244 mol), followed by reaction at room temperature for 20 to 22 hours after the dropwise addition (0.4 g, 0.00203 mol) After the reaction, triethylamine was removed, methanol and excess sodium carbonate were added to the crude product, followed by stirring at room temperature for 24 to 26 hours. After completion of the reaction, methanol was removed, and petroleum ether and ethyl acetate (the volume ratio of the two was 4: 1) as a eluent,Separation by chromatography column to obtain pureTris (4-acetophenylene)amine. |