Structure of 102664-66-4
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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.
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CAS No. : | 102664-66-4 |
Formula : | C24H21N3 |
M.W : | 351.44 |
SMILES Code : | C1(NC2=CC=CC=C2)=CC(NC3=CC=CC=C3)=CC(NC4=CC=CC=C4)=C1 |
MDL No. : | MFCD01463903 |
InChI Key : | BMQHYGLEATWRFO-UHFFFAOYSA-N |
Pubchem ID : | 227820 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 27 |
Num. arom. heavy atoms | 24 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 115.07 |
TPSA ? Topological Polar Surface Area: Calculated from |
36.09 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.35 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
6.55 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
6.92 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.0 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.27 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
5.22 |
Log S (ESOL):? ESOL: Topological method implemented from |
-6.41 |
Solubility | 0.000138 mg/ml ; 0.000000392 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-7.11 |
Solubility | 0.0000275 mg/ml ; 0.0000000783 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-10.06 |
Solubility | 0.0000000305 mg/ml ; 0.0000000001 mol/l |
Class? Solubility class: Log S scale |
Insoluble |
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) |
Yes |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-3.79 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 |
1.0 |
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 |
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) |
3.05 |
* 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 |
---|---|---|
34% | With potassium dichromate; sulfuric acid; In water; acetone; at 40 - 50℃; for 1h; | Amixture of 1,3,5-tris(phenylamino)benzene 9 (382 mg, 1.10 mmol)and N-phenyl-p-phenylenediamine (200 mg, 1.10 mmol) in water andacetone (150 mL/100 mL) with cH2SO4 (6 drops, 0.3 mL) were treatedwith K2Cr2O7 (320 mg, 1.10 mmol) and heated at 40-50 C for 1 hwith stirring in a beaker covered with a petri dish. The petri dish wasthen removed and heating and stirring continued for a further 2-3 hto evaporate the acetone. The acetone must be evaporated before themixture is filtered. After allowing to cool the mixture was filteredthrough a fine pore sinter and washed with H2O. The precipitate wasextracted with MeOH (6 × 50 mL) in the sinter each time agitatingthe precipitate. The combined MeOH extracts were evaporated to dryness then purified by chromatography on silica gel. After elutionwith MeOH, elution with cNH3/MeOH (20/80) gave the title compound(198 mg, 34%) as a dark blue solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With potassium dichromate; sulfuric acid; In water; acetone; at 40 - 50℃; for 1h; | A mixture of1,3,5-tris(phenylamino)benzene 95 (382 mg, 1.10 mmol) andp-phenylenediamine (118 mg, 1.10 mmol) in water and acetone(150 mL/100 mL) with cH2SO4 (six drops, 0.3 mL) was treated withK2Cr2O7 (320 mg, 1.10 mmol) and heated at 40-50 C for 1 h withstirring in a beaker covered with a petri dish. The petri dish was thenremoved and heating and stirring continued for a further 2-3 h toevaporate the acetone. The acetone must be evaporated before themixture is filtered. After allowing the mixture to cool it was filteredthrough a fine pore sinter and washed with H2O. The precipitate wasextracted with MeOH (6 × 50 mL) in the sinter each time agitatingthe precipitate. The combined MeOH extracts were evaporated todryness then purified by chromatography on silica gel. After elutionwith MeOH elution with cNH3/MeOH (20/80) gave the title compound(194 mg, 35%) as a dark purple glistening solid, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With hydrogenchloride; In ethanol; water; for 3h; | 1,3,5-tris(Phenylamino)benzene 9 (100 mg, 0.285 mmol) and4-nitrosodiphenylamine 12 (56 mg, 0.285 mmol) in EtOH (10 mL) andcHCl (5 mL) were heated to dryness in a beaker over 3 h in a fume hood.After the addition of water the product was filtered off and purifiedby chromatography on silica gel. MeOH eluted the title compound(23 mg, 18%) as a dark green solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; for 72h;Inert atmosphere; Reflux; | A mixture of aniline (7.4 g, 79.4 mmol), 1,3,5-tribromobenzene 3 (5.0 g, 15.88 mmol), tris(dibenzylideneacetone) dipalladium(0) [Pd2(dba)3(0), 0.11 g, 0.25 mol %], rac-2,2'-bis(diphenylphosphino)-1,1'-binapthyl (BINAP, 0.22 g, 0.75 mol %), and sodium t-butoxide (7.63 g, 79.4 mmol) in anhydrous toluene (250 mL) was heated to refluxing temperature under nitrogen for a period of 72 h. The reaction mixture was cooled to room temperature and washed with water (100 mL). The organic layer was dried over anhydrous sodium sulfate (Na2SO4). After evaporation of the solvent, a crude brown color solid was obtained. Excess aniline was then removed by distillation at 130 C under reduced pressure of 101 mmHg. It was further purified by chromatography (SiO2). The resulting light brown product 1,3,5-tris(phenylamino)benzene 4, TPAB, was obtained in 75% yield (4.18 g). FT-IR (KBr) upsilonmax 3403 (m), 3375 (m), 3078 (w), 3019 (w), 2945 (s), 1612 (m), 1591 (vs), 1518 (m), 1496 (s), 1469 (m), 1431(w), 1456 (m), 1409 (m), 1365 (w), 1295 (m), 1269 (w), 1246 (m), 1,171 (m), 1073 (w), 1030 (w), 897 (w), 834 (w), 820 (w), 802 (w), 756 (m), 721 (w), 700 (m), 688 (m), 613 (w), and 558 (w) cm-1; UV-vis (CHCl3, 1.0 × 10-5 M) lambdamax (epsilon) 289 nm (4.80 × 104 L mol-1 cm-1); 1H-NMR (500 MHz, CDCl3) delta 7.25 (t, J = 7.8 Hz, 6H), 7.08 (d, J = 7.7 Hz, 6H), 6.92 (t, J = 7.3 Hz, 3H), 6.32 (s, 3H), and 5.60 (s, 3H, N-H); 13C-NMR (125 MHz, CDCl3) delta 145.4, 142.7, 129.3, 121.3, 118.7, and 99.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; for 72h;Inert atmosphere; Reflux; | A mixture of 2-bromo-9,9-bis(3',5',5'-trimethyl-1'-hexyl)fluorene (8.39 g, 17.04 mmol, excess), <strong>[102664-66-4]1,3,5-tris(N-phenylamino)benzene</strong> (1.0 g, 2.84 mmol), tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3(0), 0.02 g, 0.25 mol %], rac-2,2'-bis(diphenylphosphino)-1,1'-binapthyl (BINAP, 0.04 g, 0.75 mol %), and sodium t-butoxide (1.63 g, 17.04 mmol) in anhydrous toluene (75 mL) was heated to refluxing temperature under nitrogen for a period of 72 h. The reaction mixture was cooled to room temperature and washed with water (50 mL). The organic layer was dried over anhydrous sodium sulfate. After evaporation of the solvent, it afforded a crude brown colored paste. The paste was subjected to column chromatography purification using silica gel as the stationary phase and hexane-ethyl acetate(9:1) as the eluent, to afford N1,N3,N5-tris(9,9-di(3',5',5'-trimethyl-1'-hexyl)fluoren-2-yl)-1",3",5"-tris(phenylamino)-benzene, tris(DPAF-C9) 7, as light yellow solids or clear thick sticky gel-like paste, while residual solvents are present, in 88% yield (3.98 g). FT-IR (KBr) upsilonmax 3,063 (w, aromatic C-H stretching), 3,037 (w), 3,019 (w), 2,953 (vs, aliphatic C-H stretching), 2,865 (s), 1,583 (s, C=C), 1500 (s), 1,493 (s, anti-symmetric deformations of CH3 groups and scissor vibrations of CH2 groups), 1,450, 1392 (w), 1363 (m, symmetric deformations of CH3 groups), 1294 (m, asymmetric stretching vibrations of C-N-C), 1249 (w, asymmetric stretching vibrations of C-N-C), 1212 (w), 1178 (w), 1155 (w), 1037 (w), 1006 (w), 933 (w), 878 (w), 826 (w), 756 (w), 738 (s, C-H out-of-plan deformation), 711 (m, C-H out-of-plan deformation), 693 (m), 628 (w), and 510 (w) cm-1; UV-vis (CHCl3, 1.0 × 10-5 M) lambdamax (epsilon) 323 (5.71 × 104) and 348 nm (5.66 × 104 L mol-1 cm-1); PL (CHCl3,1.0 × 10-5 M) lambdaem,max 390.1 nm; 1H-NMR (500 MHz, CDCl3) delta 7.57 (s, 3H, br), 7.51 (d, J = 7.5 Hz, 3H), 7.32-7.21 (m, 9H), 7.09-7.01 (m, 18H), 6.82 (t, J = 7.2 Hz, 3H), 6.55 (s, 3H, br), 1.92-1.67 (m, 12H), 1.11 (s, 6H), and 0.97-0.39 (m, 96H); 13C-NMR (125 MHz, CDCl3) delta 151.9, 150.4, 149.3, 147.6, 146.5, 141.0, 136.5, 128.9, 126.7, 126.3, 123.7, 122.7, 121.9, 120.2, 119.1, 115.6, 54.7, 50.9, 50.63, 50.57, 38.0, 37.9, 37.6, 37.5, 33.1, 32.8, 30.9, 30.0, 29.5, 29.3, 27.3, 22.7, and 22.5; MALDI-TOF MS calcd for C117H153N3, m/z 1600.2; found, m/z 1601.6 (MH+). |
83% | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; for 72h;Reflux; Inert atmosphere; | Synthetic procedure of tris(DPAF-C9) was followed by and slightly modified from the recently reported methods [22]. A typical procedure was given as follows. A mixture of BrF-C9 (10.0 g,20.3 mmol, excess), TPAB (1.16 g, 3.30 mmol), Pd2(dba)3(0) (0.023 g, 0.25 mol%), BINAP (0.046 g,0.75 mol%), and sodium t-butoxide (1.94 g, 20.3 mmol) taken in anhydrous toluene (75 mL) was heated to refluxing temperature under nitrogen for a period of 72 h. After being cooled to roomtemperature, the reaction mixture was washed with water for three times and dried over sodium sulfate. A crude brown colored paste was obtained after evaporating the solvent. It was subjected to column chromatography purification using silica gel as the stationary phase and hexane-ethylacetate(9:1) as the eluent. The product of tris(DPAF-C9) was collected at Rf = 0.8 as light yellow solids in 83%yield (4.35 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; for 72h;Inert atmosphere; Reflux; | A mixture of 2-bromo-9,9-bis(3',5',5'-trimethyl-1'-hexyl)fluorene (0.71 g, 1.42 mmol), 1,3,5-tris(phenylamino)benzene (0.25 g, 0.71 mmol), tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3(0), 0.005 g, 0.25 mol %], rac-2,2'-bis(diphenylphosphino)-1,1'-binapthyl (BINAP, 0.01 g, 0.75 mol %), and sodium t-butoxide (0.70 g, 7.10 mmol) in anhydrous toluene (50 mL) was heated to refluxing temperature under nitrogen for 72 h. The reaction mixture was cooled to room temperature and washed with water (30 mL). The organic layer was dried over anhydrous sodium sulfate. After evaporation of the solvent, it afforded a crude brown colored semi-solid. It was purified by column chromatography using silica gel as the stationary phase and hexane-ethylacetate (9:1) as the eluent to afford N1,N3-bis(9,9-di(3',5',5'-trimethyl-1'-hexyl)fluoren-2-yl)-1",3",5"-tris(phenylamino)benzene, bis(DPAF-C9) 6, as whiteto light yellow glassy solids in 52% yield (0.43 g). FT-IR (KBr) upsilonmax 3402 (m), 3062 (w), 3036 (w), 3010 (w), 2953 (s), 2865 (m), 1585 (s), 1492 (s), 1467 (m), 1450 (m), 1,422 (w), 1392 (m), 1363 (w), 1299 (m), 1252 (m), 1213 (w), 1155 (w), 1079 (w), 1033 (w), 824 (w), 738 (m), 711 (w), 693 (m), and 512 (w) cm-1;UV-vis (CHCl3, 1.0 × 10-5 M) lambdamax (epsilon) 308 (5.56 × 104) and 348 nm (5.07 × 104 L mol-1 cm-1); PL (CHCl3,1.0 × 10-5 M) lambdaem,max 390.8 nm; 1H-NMR (500 MHz, CDCl3) delta 7.61-7.58 (m, 4H), 7.34-7.21 (m, 7H), 7.16(t, J = 7.2 Hz, 4H), 7.12-7.01 (m, 10H), 6.90 (t, J = 6.8 Hz, 1H), 6.86-6.83 (m, 2H), 6.74 (t, J = 6.5 Hz, 1H), 6.53 (s, 1H), 6.42 (s, 2H), 5.51 (s, 1H), 1.98-1.71 (m, 8H), 1.21-1.07 (s, 4H, br), 0.97-0.86 (d, 4H), and ,0.83-0.34 (m, 60H); 13C-NMR (125 MHz, CDCl3) delta 151.9, 150.5, 149.6, 147.8, 146.7, 142.5, 141.0, 136.6, 129.1, 129.0, 126.7, 126.3, 124.1, 123.1, 122.7, 122.0, 120.6, 120.2, 119.1, 117.2, 112.8, 108.10, 108.0, 100.0, 54.8, 50.9, 50.7, 38.0, 37.9, 37.7, 37.6, 33.1, 32.9, 30.9, 29.9, 29.5, 29.30, 29.27, 27.3, 22.6, and 22.5; MALDI-TOF MS calcd for C86H109N3, m/z 1,183.9; found, m/z 1,184.9 (MH+). |
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