Structure of 4-Benzyloxyphenylboronic acid
CAS No.: 146631-00-7
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CAS No. : | 146631-00-7 |
Formula : | C13H13BO3 |
M.W : | 228.05 |
SMILES Code : | OB(O)C1=CC=C(OCC2=CC=CC=C2)C=C1 |
MDL No. : | MFCD01075705 |
InChI Key : | DMJHEIDWSIAXCS-UHFFFAOYSA-N |
Pubchem ID : | 2734314 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.08 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 67.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.69 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.79 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.54 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.77 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.08 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.95 |
Solubility | 0.253 mg/ml ; 0.00111 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.97 |
Solubility | 0.244 mg/ml ; 0.00107 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.96 |
Solubility | 0.0251 mg/ml ; 0.00011 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) |
No |
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 |
-6.07 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 |
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) |
1.98 |
* 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 |
---|---|---|
2-(4-Benzyloxyphenyl)-5-(6-octyloxypyridin-3-yl)pyrazine STR50 Step 1 In accordance with scheme C-I, 30 g (201 mmol) of <strong>[19745-07-4]2,5-dichloropyrazine</strong> and 45.92 g (201 mmol) of 4-benzyloxyphenylboronic acid are coupled analogously to Example 4a to give 2-chloro-5-(4-benzyloxyphenyl)pyrazine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxygen; triethylamine;copper diacetate; In dichloromethane; at 20℃; for 16h; | Description 19. 4-bromo-6-fluoro-1-{4-[(phenylmethyl)oxy]phenyl}-1H-indole A mixture of 4-bromo-6-fluoro-1 H-indole (D16),(200 mg, 0.935 mmol), 4- benzyloxyphenylboronic acid (426 mg, 1.87 mmol), copper (II) acetate (332 mg, 1.87 mmol) and triethylamine (0.26 ml_, 188 mg, 1.87 mmol) in dichloromethane (5 ml.) was stirred in air at room temperature for 16 hours. The mixture was filtered through celite, concentrated and purified by chromatography on silica gel (elution with 0-20percent ethyl acetate in hexanes) to give the tite compound as a pink solid (D19), (205 mg). LC-MS: MH+ = 396/398 (C21H15BrFNO = 395/397) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17.4 g | With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; triethylamine; triphenylphosphine; In 1,4-dioxane; water; for 2h;Inert atmosphere; Reflux; | 4?-benzyloxy-biphenyl-3,5-dicarboxylic acid is prepared from commercially available [4-(benzyloxy)phenyl]-boronic acid and <strong>[23351-91-9]5-bromo-isophthalic acid</strong>. To a solution of sodium carbonate (31.26 g, 295.0 mol) in dist. water (135 ml) is added 1,4-dioxane (210 ml), <strong>[23351-91-9]5-bromo-isophthalic acid</strong> (14.46 g, 59.0 mmol) and [4-(benzyloxy)phenyl]-boronic acid (14.82 g, 65.0 mol) followed by bis(triphenylphosphine)palladium(II) dichloride (0.83 g, 1.2 mmol), triphenylphosphine (0.31 g, 1.2 mmol) and triethylamine (0.12 g, 1.2 mmol) under nitrogen atmosphere. The reaction mixture is heated at reflux for 2 hs. After cooling to room temperature 400 ml dist. water is added, and the reaction mixture is neutralized with conc. HCl acid under cooling to pH1. The precipitated crude product is filtrated, washed with dist. water, and further purified by recrystallization from acetonitrile to provide gray crystals of 4?-benzyloxy-biphenyl-3,5-dicarboxylic acid (17.4 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With palladium diacetate; potassium carbonate; triphenylphosphine; In water; N,N-dimethyl-formamide; at 100℃; for 3h;Microwave irradiation; Inert atmosphere; Sealed tube; | <strong>[16870-28-3]2-hydroxy-4-iodobenzoic acid</strong> (50 mg, 0.189 mmol), acid 4-(benzyloxy)phenylboronic (51.8 mg, 0.227 mmol), PPh3 (7.4 mg, 0.028 mmol), K2CO3 (91.4 mg, 0.662 mmol), Pd(AcO)2 (2.12 mg, 0.0095 mmol), 1:1 DMF: H2O (2 ml) were used. In this case, prior to chromatographic purification, the residue from evaporating the filtrate was resuspended in acetonitrile. The precipitate was separated from the liquid phase and the latter was discarded. The solid was then purified by flash chromatography (elution with AcOEt: CH3CN:H2O:CH3OH 60:10:10:10 mixture). 95 was obtained in the form of a white solid. Yield after purification: 100 % (62 mg). 1H NMR (400 MHz, acetone-d6) delta 7.93 (d, J = 8.3 Hz, 1H), 7.70 (m, 2H), 7.51 (m, 2H), 7.41 (m, 2H), 7.34 (m, 1H), 7.23 (dd, J = 8.28, 1.82 Hz, 1H), 7.19 (d, J = 1.8 Hz, 1H), 7.14 (m, 2H), 5.21 (s, 2H). 13C NMR (101 MHz, acetone-d6) delta 172.5 (CO), 163.3 (C), 160.4 (C), 149.0 (C), 138.2 (C), 132.7 (C), 131.8(CH), 129.3 (CH), 129.2 (CH), 128.7 (CH), 128.5 (CH), 118.3 (CH), 116.2 (CH), 115.2 (CH), 111.4 (C), 70.6 (CH2). HRMS (TOF, ES-): Calculated for C20H15O4: (M-H)-: m/z 319.0970. 319.0964 found (deviation 1.9 ppm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With pyridine; oxygen; In dichloromethane; at 20℃; for 48.0h;Molecular sieve; | A mixture of <strong>[126937-43-7]1-benzyl 2-methyl piperazine-1,2-dicarboxylate</strong> (2 g, 7.19 mmol), (4-(benzyloxy)phenyl)boronic acid (3.3 g, 14.37 mmol) and copper (II) acetate (1.30 g, 7.19 mmol) in dichloromethane (60 mL) was added pyridine (1.2 mL, 14.37 mmol) and 2 g of 4A molecular sieves. The reaction mixture was stirred at room temperature for 48 h under oxygen atmosphere. The resulting suspension was filtered through Celite pad, washed with 50 mL of dichloromethane and filtrate was evaporated under reduced pressure to give the crude residue. The crude residue was purified by flash chromatography (0 - 10% EtOAc in pet ether) to afford 1-benzyl 2-methyl 4-(4- (benzyloxy)phenyl)piperazine-1,2-dicarboxylate (2.2 g, 8.90 mmol, 40% yield) as off- white solid. LC-MS, [M+H]+= 461.1, (Method F, tR= 3.37 min).1H NMR (300MHz, CDCl3): δ ppm 7.48 - 7.29 (m, 10H), 6.97 - 6.84 (m, 4H), 5.27 - 5.16 (m, 2H), 5.07 - 5.00 (m, 2H), 4.96 - 4.77 (m, 1H), 4.16 - 3.93 (m, 2H), 3.77 (s, 3H), 3.51 - 3.23 (m, 2H), 2.93 - 2.65 (m, 2H). (Mixture of rotamers). |
40% | With pyridine; oxygen; In dichloromethane; at 20℃; for 48.0h;Molecular sieve; | A mixture of <strong>[126937-43-7]1-benzyl 2-methyl piperazine-1,2-dicarboxylate</strong> (2 g, 7.19 mmol), (4-(benzyloxy)phenyl)boronic acid (3.3 g, 14.37 mmol) and copper (II) acetate (1.30 g, 7.19 mmol) in dichloromethane (60 mL) was added pyridine (1.2 mL, 14.37 mmol) and 2 g of 4A molecular sieves. The reaction mixture was stirred at room temperature for 48 h under oxygen atmosphere. The resulting suspension was filtered through Celite pad, washed with 50 mL of dichloromethane and filtrate was evaporated under reduced pressure to give the crude residue. The crude residue was purified by flash chromatography (0 - 10% EtOAc in pet ether) to afford 1-benzyl 2-methyl 4-(4- (benzyloxy)phenyl)piperazine-1,2-dicarboxylate (2.2 g, 8.90 mmol, 40% yield) as off- white solid. LC-MS, [M+H]+= 461.1, (Method F, tR= 3.37 min).1H NMR (300MHz, CDCl3): δ ppm 7.48 - 7.29 (m, 10H), 6.97 - 6.84 (m, 4H), 5.27 - 5.16 (m, 2H), 5.07 - 5.00 (m, 2H), 4.96 - 4.77 (m, 1H), 4.16 - 3.93 (m, 2H), 3.77 (s, 3H), 3.51 - 3.23 (m, 2H), 2.93 - 2.65 (m, 2H). (Mixture of rotamers). |
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