Structure of 66217-20-7
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CAS No. : | 66217-20-7 |
Formula : | C14H15BrO |
M.W : | 279.17 |
SMILES Code : | CCCCOC1=CC2=CC=C(Br)C=C2C=C1 |
MDL No. : | MFCD01568860 |
InChI Key : | LIQQRPRDWMYCPK-UHFFFAOYSA-N |
Pubchem ID : | 3798414 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.29 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 72.56 |
TPSA ? Topological Polar Surface Area: Calculated from |
9.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.4 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.09 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.3 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.45 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.98 |
Solubility | 0.00295 mg/ml ; 0.0000106 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.03 |
Solubility | 0.00262 mg/ml ; 0.0000094 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.26 |
Solubility | 0.000152 mg/ml ; 0.000000545 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
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 |
-4.39 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.72 |
* 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 |
---|---|---|
2.31 g (92%) | A. 2-Bromo-6-butoxynaphthalene An oil dispersion of 480 mg (50%, 10 mmol, Alfa) of sodium hydride was washed three times with petroleum ether then the residue covered with 5 ml of dry THF. To the resulting stirred slurry was added dropwise a solution of 2.00 g (8.97 mmol, Aldrich) of 6-bromo-2-naphthol, in 10 ml of THF over 10 minutes. The reaction mixture was stirred for 30 minutes then 1.70 g (9.23 mmol, Aldrich) of 1-iodobutane and 15 ml of sieve-dried DMF were added. The resulting solution was heated to 60 for two hours, then cooled, added to 100 ml of H2 O and extracted with 50 ml of petroleum ether. The organic extract was washed with an additional 100 ml of H2 O, dried (MgSO4) and concentrated in vacuo to give a solid. The crude material was purified by flash chromatography (15*5 cm, pet ether) to afford 2.31 g (92%) of title compound as a white solid, m.p. 48-50. 60 MHz 1 H NMR (CDCl3) 0.73-2.20 (m, H, --(CH2)2 CH3) 4.05 (t, J=6, 2H, --OCH2 --) 7.00-8.00 (m, 6H, aromatic) TLC: Rf (silica gel, 1:9 Et2 O/pet ether)=0.63, PMA and UV, homogeneous | |
2.31 g (92%) | A. 2-Bromo-6-butoxynaphthalene An oil dispersion of 480 mg (50%, 10 mmol, Alfa) of sodium hydride was washed three times with petroleum ether then the residue covered with 5 ml of dry THF. To the resulting stirred slurry was added dropwise a solution of 2.00 g (8.97 mmol, Aldrich) of 6-bromo-2-naphthol, in 10 ml of THF over 10 minutes. The reaction mixture was stirred for 30 minutes then 1.70 g (9.23 mmol, Aldrich) of 1-iodobutane and 15 ml of sieve-dried DMF were added. The resulting solution was heated to 60 for two hours, then cooled, added to 100 ml of H2 O and extracted with 50 ml of petroleum ether. The organic extract was washed with an additional 100 ml of H2 O, dried (MgSO4) and concentrated in vacuo to give a solid. The crude material was purified by flash chromatography (15*5 cm, pet ether) to afford 2.31 g (92%) of title compound as a white solid, m.p. 48-50. 60 MHz 1 H NMR (CDCl3) 0.73-2.20 (m, 7H, --(CH2)2 CH3), 4.05 (t, J=6, 2H, --OCH2 --), 7.00-8.00 (m, 6H, aromatic). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Benzophenone imine; tris-(dibenzylideneacetone)dipalladium(0); potassium-t-butoxide; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 100℃; for 3.0h;Inert atmosphere; | Under N2, to a solution of 2- bromo-6-butoxynaphthalene (1.2 g, 4.30 mmol) in toluene (20 mL) was added diphenylmethanimine (0.94 g, 5.10 mmol), t-BuOK (1.45 g, 12.90 mmol), BINAP (1.07 g, 1.70 mmol) and Pd2(dba)3 (0.79 g, 0.80 mmol). The reaction mixture was stirred at 100C for 3 h. The reaction mixture was cooled to rt and H2O (100 mL) was added, extracted with EtOAc (40 mL x 3) and the combined organic phases were washed with brine (20 mL x 3), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue in TFA (30 mL) was refluxed for 18 h. The solvent was removed under reduced pressure. NaHCO3 (aq.) (100 mL) was added and extracted with EtOAc (50 mL x 3). The combined organic phases were washed with brine (10 mL x 3), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by Flash chromatography (eluent: 50% EtOAc in PE) to afford 6-butoxynaphthalen-2-amine (0.845 g, 94% purity, 86% yield) as a yellow oil. [M +H] + m/z 216.13, found 216.05. | |
With Benzophenone imine; tris-(dibenzylideneacetone)dipalladium(0); potassium-t-butoxide; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 100℃; for 3.0h;Inert atmosphere; | Under N2, to a solution of 2- bromo-6-butoxynaphthalene (1.2 g, 4.30 mmol) in toluene (20 mL) was added diphenylmethanimine (0.94 g, 5.10 mmol), t-BuOK (1.45 g, 12.90 mmol), BINAP (1.07 g, 1.70 mmol) and Pd2(dba)3 (0.79 g, 0.80 mmol). The reaction mixture was stirred at 100C for 3 h. The reaction mixture was cooled to rt and H2O (100 mL) was added, extracted with EtOAc (40 mL x 3) and the combined organic phases were washed with brine (20 mL x 3), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue in TFA (30 mL) was refluxed for 18 h. The solvent was removed under reduced pressure. NaHCO3 (aq.) (100 mL) was added and extracted with EtOAc (50 mL x 3). The combined organic phases were washed with brine (10 mL x 3), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by Flash chromatography (eluent: 50% EtOAc in PE) to afford 6-butoxynaphthalen-2-amine (0.845 g, 94% purity, 86% yield) as a yellow oil. [M +H] + m/z 216.13, found 216.05. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.1% | With triphenylphosphine; 1,1'-(azodicarboxylic)dipiperidide; In tetrahydrofuran; at 0 - 20℃; for 18.0h;Inert atmosphere; | Under N2, to a solution of ADDP (2.27 g, 9.00 mmol) in THF (15 mL) at 0C was added triphenylphosphine (2.36 g, 9.00 mmol) dropwise and the mixture was kept stirring for additional 25 mins. Then, 6- bromonaphthalen-2-ol (1) (1 g, 4.5 mmol) and butan-1-ol (0.4 g, 5.3 mol) in THF (2 mL) was added slowly. The reaction mixture was stirred at room temperature for 18 h. H20 (100 mL) was added, extracted with EtOAc (50 mL x 3) and the combined organic phases were washed with brine (60 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography (eluent: 10% EtOAc in PE) to afford 2- bromo-6-butoxynaphthalene (1.2 g, 95% purity, 91.1% yield) as ayellow solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ 8.10 (d, J= 1.6 Hz, 1 H), 7.79 (dd, J= 17.1, 8.9 Hz, 2 H), 7.55 (dd, J= 8.7, 1.9 Hz, 1 H), 7.35 (d, J= 2.3 Hz, 1 H), 7.20 (dd, J= 9.0, 2.4 Hz, 1 H), 4.08 (t, J = 6.5 Hz, 2 H), 1.83-1.71 (m, 2 H), 1.54-1.41 (m, 2 H), 0.95 (t, J= 7.4 Hz, 3 H). |
91.1% | With triphenylphosphine; 1,1'-(azodicarboxylic)dipiperidide; In tetrahydrofuran; at 0 - 20℃; for 18.0h;Inert atmosphere; | Under N2, to a solution of ADDP (2.27 g, 9.00 mmol) in THF (15 mL) at 0C was added triphenylphosphine (2.36 g, 9.00 mmol) dropwise and the mixture was kept stirring for additional 25 mins. Then, 6- bromonaphthalen-2-ol (1) (1 g, 4.5 mmol) and butan-1-ol (0.4 g, 5.3 mol) in THF (2 mL) was added slowly. The reaction mixture was stirred at room temperature for 18 h. H20 (100 mL) was added, extracted with EtOAc (50 mL x 3) and the combined organic phases were washed with brine (60 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography (eluent: 10% EtOAc in PE) to afford 2- bromo-6-butoxynaphthalene (1.2 g, 95% purity, 91.1% yield) as ayellow solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ 8.10 (d, J= 1.6 Hz, 1 H), 7.79 (dd, J= 17.1, 8.9 Hz, 2 H), 7.55 (dd, J= 8.7, 1.9 Hz, 1 H), 7.35 (d, J= 2.3 Hz, 1 H), 7.20 (dd, J= 9.0, 2.4 Hz, 1 H), 4.08 (t, J = 6.5 Hz, 2 H), 1.83-1.71 (m, 2 H), 1.54-1.41 (m, 2 H), 0.95 (t, J= 7.4 Hz, 3 H). |
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