Structure of 5433-01-2
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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. : | 5433-01-2 |
Formula : | C9H11Br |
M.W : | 199.09 |
SMILES Code : | CC(C1=CC(Br)=CC=C1)C |
MDL No. : | MFCD01318112 |
InChI Key : | GBSGGFCCQZUXNB-UHFFFAOYSA-N |
Pubchem ID : | 138499 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.72 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.66 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.17 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.98 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.08 |
Solubility | 0.0166 mg/ml ; 0.0000833 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.88 |
Solubility | 0.0263 mg/ml ; 0.000132 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.08 |
Solubility | 0.0167 mg/ml ; 0.0000838 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
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 |
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) |
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 |
-4.55 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 |
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) |
1.31 |
* 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 |
---|---|---|
88% | With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In toluene; for 12h;Heating / reflux; | Preparation Example 1-1: Preparation of 4-t-butyl-N- (4- isopropylphenyl ) benzenamine; As represented below in Reaction Scheme 1, 25g of 3-t- butylaniline (0.125mol) and 37.3g of 3-bromoisopropylbenzene(0.25mol) were dissolved in 25OmL of toluene, and 3.43g ofPd2(dba)3 (0.0037mol) was added thereto under a nitrogen atmosphere. Then, 14.4g of NaOBufc (0.15mol) and 1.157g of (t- Bu)3P (0.0075mol) were added to the reaction solvent, and the reaction mixture was refluxed and stirred for 12 hours. The reaction mixture was checked for the completion of the reaction by means of TLC, and if the reaction was completed, the reaction product was cooled down to room temperature. The reacted solution was poured onto a thin silica pad to perform short chromatography, and then was washed with methylene chloride (MC) . The washed solution was subjected to distillation under reduced pressure to thereby remove the solvent, and was chromatographed using n-hexane to thereby obtain a desired white solid product (29.4g, 88percent). [Reaction Scheme 1] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation of sulfonyl chlorides:Preparation of 5-(3-Isopropyl-phenyl)-pyridine-2-sulfonyl chloride; 3-Isopropyl-phenylboronic acid; n-BuLi (7.7 mL, 14.0 mmol) was added dropwise to a stirred solution of 1-bromo-3-isopropyl-benzene (2.4 g, 12.1 mmol) in dry THF (40 mL) over 30 min at -70 C. under nitrogen. The reaction mixture was degassed for 15 min, and triisopropylborate (2.63 g, 14.0 mmol) was added at the same temperature. The reaction mixture was gradually warmed to 0 C. during 90 min and stirred for an additional 30 min at 0 C. The reaction mixture was then cooled to -20 C., and an aqueous solution of 2N HCl (20 mL) was added slowly. THF was distilled off and the reaction mixture was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried over Na2SO4, and concentrated in vacuo to obtain the crude product (1.85 g, 93.5%), which was used for the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Into a 500-mL round-bottom flask purged and maintained with an inert atmosphere of N2 was placed a solution of 1-bromo-3- (propan-2-yl)benzene (5.0 g, 25.11 mmol, 1.00 equiv) in THF (250 mL). This was followed by the addition of n-BuLi (20 mL, 2.00 equiv) dropwise with stirring at -60 C. The mixture was stirred at -60C for 30 mm. To this was added N-methoxy-N-methylacetamide (3.9 g, 37.82 mmol, 1.50 equiv) dropwise with stirring at -30 C. The resulting solution was stirred for 3 h at -30 C in a liquid N2 bath. The reaction was then quenched by the addition of 20 mL of water. The resulting solution was diluted with 200 mL of EtOAc, washed with 2x100 mL of brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was applied onto a silica gel column with EtOAc/petroleum ether (1:10). This resulted in 2.7 g (66%) of the title product as colorless oil. | |
To a solution of 1 -bromo-3-isopropylbenzene (10 g, 0.05 moi) in THF was added dropwise with BuLi (47 ml,, 0.075 niol) at -60 'C. After stirred 30 minutes, N-methoxy-N-methyiacetamide (6.22 g, 0.06 mol) was added. The mixture was stirred at -30C for 3 hours. Then the mixture was quenched with H20, the mixture was partitioned between EtOAc and water. The layer was separated and washed with water, brine, dried over Na2SC>4, and concentrated. The residue was purified by column chromatography to obtained the titled compound. ? NMR (CHLQRQFORM-d): delta 7.85 (s, i l l ). 7.79 (dt, j = 7.6, 1 .4 Hz, 1H), 7.33 - 7.53 (m, 2H), 3.00 (dt, J - 13.8, 6.9 Hz, 1H), 1.30 (d, J - 6.7 Hz, 6H) | ||
To a solution of l-bromo-3-isopropylbenzene (10 g, 0.05 niol) in THF was added dropwise with BuLi (47 mL, 0.075 mol) at -60C. After stirred 30 minutes, -methoxy- -methylacetamide (6,22 g, 0.06 mol) was added. The mixture was stirred at -30C for 3 hours. Then the mixture was quenched with H20, the mixture was partitioned between EtOAc and water. The layer was separated and washed with water, brine, dried over Na2S04, and concentrated. The residue was purified by column chromatography to obtained the titled compound. 'H NMR (CHLOR OFQRM-d) : delta 7.85 (s, 1H), 7.79 (dt, J = 7.6, 1.4 Hz, 1H), 7.33 - 7.53 (m, 2H), 3.00 (dt, J - 13.8, 6.9 Hz, 1H), 1.30 (d, J - 6.7 Hz, 6H) LC-MS : m/z 163(M+H)+ |
To a solution of Compound 59A (3.96 g, 20 mmol) in dry THF (20 mL) at - 78 C was dropped a solution of n-BuLi in THF (2.5 M, 8 mL, 18 mmol). After stirred at - 78 C for 1 hour, to the mixture was dropped N-methoxy-N-methylacetamide (1.87 g, 18 mmol). The mixture was stirred at -78 C for 0.5 hour, quenched with water (10 mL), and extracted with ethyl acetate (20 mL x 3). The combined organic layers was washed with brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, from 0% to 8% v/v) to yield Compound 59B: LC-MS (ESI) m/z: 163 [M+H]+;1H-NMR (CDCl3, 400 MHz): delta (ppm) 1.27 (d, J =7.2.4 Hz, 6H), 2.60 (s, 3H), 2.93-3.00 (m, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.44 (t, J = 7.2Hz, 1H), 7.76 (d, J = 7.2 Hz, 1H), 7.83 (s, 1H). |
A194017 [22385-77-9]
1-Bromo-3,5-di-tert-butylbenzene
Similarity: 0.94
A194017 [22385-77-9]
1-Bromo-3,5-di-tert-butylbenzene
Similarity: 0.94