Structure of 18282-51-4
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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. : | 18282-51-4 |
Formula : | C7H7IO |
M.W : | 234.03 |
SMILES Code : | OCC1=CC=C(I)C=C1 |
MDL No. : | MFCD01732720 |
Boiling Point : | No data available |
InChI Key : | CNQRHSZYVFYOIE-UHFFFAOYSA-N |
Pubchem ID : | 29012 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 45.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.01 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.63 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.46 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.66 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.13 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.9 |
Solubility | 0.297 mg/ml ; 0.00127 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.92 |
Solubility | 2.84 mg/ml ; 0.0121 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.18 |
Solubility | 0.153 mg/ml ; 0.000655 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 |
-6.4 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) |
1.57 |
* 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 |
---|---|---|
With copper; potassium carbonate; | Step 1 5-Chloro-1-(4-hydroxymethyl-phenyl)-1H-pyridin-2-one <strong>[4214-79-3]5-Chloro-2-pyridinol</strong> (0.61 g, 4.7 mmol), 4-iodobenzyl-alcohol (1.00 g, 4.27 mmol), Copper (0.27 g, 4.27 mmol) and K2CO3 (0.65 g, 4.70 mmol) were heated at 180° C. for 16 hrs. The brown reaction mixture was cooled, diluted with EtOAc and washed with saturated NaHCO3. The aqueous layer was extracted with EtOAc (2*) and the combined organic extracts were washed with brine, dried (Na2SO4) and evaporated in vacuo. The residue was chromatographed (silica gel, EtOAc as eluent) to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD) delta 7.74 (d,J=2.7 Hz, 1H), 7.59 (dd, J=3.0 and 9.6 Hz, 1H), 7.51 (d, J=8.6 Hz, 2H), 7.37 (d, J=8.4 Hz, 2H), 6.61 (d, J=9.4 Hz, 1H) and 4.67(s,1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper; | Step 1 5-Chloro-1-(4-hydroxymethyl-phenyl)-1H-pyridin-2-one <strong>[4214-79-3]5-Chloro-2-pyridinol</strong> (0.61 g, 4.7 mmol), 4-iodobenzyl-alcohol (1.00 g, 4.27 mmol), Copper (0.27 g, 4.27 mmol) and K2 CO3 (0.65 g, 4.70 mmol) were heated at 180° C. for 16 hrs. The brown reaction mixture was cooled, diluted with EtOAc and washed with saturated NaHCO3. The aqueous layer was extracted with EtOAc (2*) and the combined organic extracts were washed with brine, dried (Na2 SO4) and evaporated in vacuo. The residue was chromatographed (silica gel, EtOAc as eluent) to afford the title compound as a white solid. 1 H NMR (400 MHz, CD3 OD) delta 7.74 (d, J=2.7 Hz, 1H), 7.59 (dd, J=3.0 and 9.6 Hz, 1H), 7.51 (d, J=8.6 Hz, 2H), 7.37 (d, J=8.4 Hz, 2H), 6.61 (d, J=9.4 Hz, 1H) and 4.67(s,1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium phosphate tribasic heptahydrate; chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1'-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl tert-butyl ether; XPhos; In ethanol; at 20℃; for 0.5h; | General procedure: Method (1): Synthesis from 4-tert-butylchlorobenzene as a raw material: K3P04 · 7H20 (3.0 g, 8.85 mmol) and bis-pinacol borate (749 mg, 2.95 mmol) were sequentially added to the reaction flask.The catalyst-chloro (2-dicyclohexyl phosphino-2 ', 4', 6'-tri - triisopropyl-1,1'-biphenyl) (1,1'-biphenyl -2-amino-2'_ -yl)palladium(II) (12 mg, 0.015 mmol) and ligand 2-dicyclohexylphosphine-2',4',6/-triisopropylbiphenyl (4 mg, 0.008 mmol), followed by EtOH (6 mL) The mixture was stirred, and p-tert-butylchlorobenzene (0.5 mL, 2.95 mmol) was added and the mixture was reacted at room temperature for 0.5 h. After the reaction was completed, the reaction mixture was diluted with ethyl acetate (2 mL) After washing with ethyl acetate (6 mL) in three portions, the filtrate was combined, and the solvent was evaporated to dryness, and the solvent was separated by silica gel (200 to 300 mesh). The eluent was petroleum ether and ethyl acetate. 10~80:1), obtained as a white solid, identified by NMR spectrum as 4-tert-butylphenylboronic acid pinacol ester, yield 98% |
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In dimethyl sulfoxide; at 85℃; for 18h;Inert atmosphere; | (IV) Synthesis of Compound (12); (4-[{4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl}(4H-1,2,4-triazol-4-yl)amino]benzonitrile); <Method A>; Compound (12) was synthesized according to the scheme below.; Here, Compound (16) was synthesized according to the scheme below.; (i) Synthesis of Compound (14) (4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl alcohol) (see Non-patent Literature 14 (Filippis, A.; Morin, C.; Thimon, C., Synth. Commun. 2002, 32, 2669-2676)); Under argon atmosphere, PdCl2(dppf)·CH2Cl2 (245 mg, 300 mumol), potassium acetate (2.94 g, 30.0 mmol) and bis(pinacolato)diboron (2.79 g, 11.0 mmol) were sequentially added to a DMSO (30 mL) solution of Compound (13) (2.34 g, 10.0 mmol) at room temperature, and the mixture was stirred at 85 C for 18 hours. The mixture was cooled to room temperature, and then water (250 mL) was added to the mixture and the mixture was extracted with ethyl acetate (100 mL × 3). All the organic phases were mixed, sequentially rinsed with water (100 mL × 3) and a saline solution (100 mL × 1), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (60 g of silica gel, n-hexane/EtOAc = 5/1) to obtain Compound (14) as a colorless solid. TLC Rf = 0.41 (n-hexane/EtOAc = 2/1) 1H NMR (300 MHz, CDCl3) delta 1.35 (s,12H,4CH3), 4.72 (s, 2H, benzylic CH2), 7.34-7.41 (AA'BB', 2H, aromatic), 7.78-7.84 (AA'BB', 2H, aromatic). |
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