Structure of 128272-29-7
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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. : | 128272-29-7 |
Formula : | C20H21BrO |
M.W : | 357.28 |
SMILES Code : | OC1=C(C2(C3)CC4CC3CC(C4)C2)C=C5C=C(Br)C=CC5=C1 |
MDL No. : | MFCD13182367 |
InChI Key : | BLOOFHRWAOQRNT-UHFFFAOYSA-N |
Pubchem ID : | 14549072 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 22 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 95.44 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
6.91 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.3 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.36 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
5.39 |
Log S (ESOL):? ESOL: Topological method implemented from |
-6.68 |
Solubility | 0.0000748 mg/ml ; 0.000000209 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-7.15 |
Solubility | 0.0000255 mg/ml ; 0.0000000714 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.37 |
Solubility | 0.000152 mg/ml ; 0.000000426 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 |
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) |
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) |
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 |
-3.57 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) |
4.33 |
* 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 |
---|---|---|
In ethanol; N,N-dimethyl-formamide; | (a) Preparation of 7-(1-adamantyl)-6-benzyloxy-2-bromonaphthalene 1.26 g (42 mmol) of sodium hydride (80% in oil) and 50 ml of DMF were introduced into a 3-necked flask, a solution of 12.5 g (35 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong> in 100 ml of DMF was added dropwise and stirring was carried out until gas evolution had ceased. 5 ml (42 mmol) of benzyl bromide were then added and stirring was carried out at room temperature for 2 hours. The reaction mixture was poured into water and extracted with ethyl ether and the organic phase was separated by settling, dried over magnesium sulfate and evaporated. The residue obtained was taken up in ethanol, heated to reflux, cooled, filtered and dried. 12.5 g (80%) of the expected compound were collected, which compound had a melting point of 150-1 C. | |
(a) Preparation of 7-(1-adamantyl)-6-benzyloxy-2-bromonaphthalene Following the basic procedure of Example 11, by reacting 12.5 g (35 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong> with 5 ml (42 mmol) of benzyl bromide, 12.5 g (80%) of the expected compound of melting point 150-151 C. were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(a) Preparation of 7-(1-adamantyl)-6-(4-fluorobenzyl)oxy-2-bromonaphthalene Following the procedure of Example 1(a), but reacting 1.1 g (3 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong> with 420 mul (3.3 mmol) of 4-fluorobenzyl bromide, 1.2 g (86%) of the expected compound were obtained in the form of a colorless oil. | ||
(a) Preparation of 7-(1-adamantyl)-6-(4-fluorobenzyl)oxy-2-bromonaphthalene Following the basic procedure of Example 11, by reacting 1.1 g (3 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong> with 420 mul (3,3 mmol) of 4-fluorobenzyl bromide, 1.2 g (86%) of the expected compound was obtained in the form of a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In diethyl ether; n-heptane; dichloromethane; | (a) Preparation of 3-(1-adamantyl)-6-bromo-2-naphthol 56 g (0.25 mol) of 6-bromo-2-naphthol, 38.2 g (0.25 mol) of 1-adamantanol and 500 ml of a mixture of dichloromethane and heptane (40/60) were introduced into a round-bottomed flask. 15 ml of concentrated sulfuric acid were added and the reaction mixture was stirred at room temperature for 48 hours. The solid was filtered off, washed with heptane (3*100 ml) and dissolved in ethyl ether and the organic phase was washed with water, separated by settling, dried over magnesium sulfate and evaporated. 60.1 g (67%) of the expected compound were collected, which compound had a melting point of 215-6 C. | |
With hydrogenchloride; In n-heptane; dichloromethane; water; | (a) Synthesis of 7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene: 22.3 g (0.1 mol) of 6-bromo-2-naphthol, 15.2 g (0.1 mol) of 1-adamantanol and 100 ml of dichloromethane were introduced into a round-bottomed flask. 5.5 ml of concentrated hydrochloric acid were added and the mixture was stirred at room temperature for twelve hours. The mixture was evaporated to dryness and the residue was taken up in water and neutralized with sodium bicarbonate. The resulting mixture was extracted with ethyl acetate and the organic phase was separated out after settling of the phases had taken place, dried over magnesium sulfate and evaporated. The residue obtained was triturated in a mixture of dichloromethane and heptane (30/70), filtered and dried. 19 g (53%) of the expected compound, with a melting point of 215-6 C., were collected. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(a) Preparation of 7-(1-adamantyl)-6-heptyloxy-2-bromonaphthalene Following the procedure of Example 8(b), but reacting 3.4 g (9.5 mmol) of 3-(1-adamantyl)-6-bromo-2-naphthol with 2.05 g (11.4 mmol) of 1-bromoheptane, 3.4 g (79%) of 7-(1-adamantyl)-6-heptyloxy-2-bromonaphthalene were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; triethylamine; In N,N-dimethyl-formamide; | Preparation of 7-(1-adamantyl)-6-tert-butyldimethylsilyloxy-2-bromonaphthalene 11.9 g (33.3 mmol) of <strong>[128272-29-7]7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene</strong>, 120 ml of DMF, 5.1 ml (36.6 mmol) of triethylamine and 203 mg of 4-dimethylaminopyridine were introduced successively into a three-necked flask. A solution of 5.52 g (36.6 mmol) of tert-butyldimethylsilyl chloride was added dropwise and the mixture was stirred at room temperature for 12 hours. The reaction medium was poured into water, extracted with ethyl ether, the organic phase decanted, dried over magnesium sulfate and evaporated. The residue obtained was purified by chromatography on a silica column eluted with heptane; 12 g (76%) of 7-(1-adamantyl)-6-tert-butyldimethylsilyloxy-2-bromonaphthalene of melting point 120-121 C. were recovered. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In hexane; n-heptane; water; ethyl acetate; | EXAMPLE 9 Preparation of 7-(1-adamantyl)-6-hydroxy-2-bromonaphthalene In a 100 ml flask, under a nitrogen atmosphere, are placed 2 g of 1-acetoxyadamantane and 20 ml of n-heptane, and 0.5 g of concentrated sulfuric acid is introduced drop by drop. At a temperature of about 22.C, 2.3 of 6-hydroxy-2-bromonaphthalene are added slowly and the mixture is left in vigorous agitation. The solvent is eliminated by filtration and the solid residue in suspension in the water is collected. The residue is filtered and then washed until neutrality is obtained. The resulting reddish solid is washed again with hexane until a colorless filtrate is obtained. After drying in a vacuum oven for 24 hours at 30 C one obtains a raw product which is chromatographed with a silica column using an ethyl acetate and hexane mixture of 1:9 as the eluent. After evaporation of the solvents, 1.3 g of desired raw product were obtained (Melting point: 218-224 C.). |
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