Structure of 7073-69-0
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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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Batch number can be found on the product's label following the word 'Batch'.
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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 7073-69-0 |
Formula : | C9H11BrO |
M.W : | 215.09 |
SMILES Code : | CC(C)(O)C1=C(Br)C=CC=C1 |
MDL No. : | MFCD00767180 |
Boiling Point : | No data available |
InChI Key : | TXQKNSQVEWHJAQ-UHFFFAOYSA-N |
Pubchem ID : | 329527 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 49.77 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.37 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.32 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.91 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.97 |
Solubility | 0.229 mg/ml ; 0.00106 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.38 |
Solubility | 0.889 mg/ml ; 0.00414 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.5 |
Solubility | 0.0674 mg/ml ; 0.000313 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 |
-5.96 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 |
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) |
1.27 |
* 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 |
---|---|---|
82% | A flask under nitrogen was charged with vinyl alcohol IV (97 g), bromo alcohol IIA (81g ), DMF (380 mL) and N,N-dicyclohexylmethylamine (Cy2NMe, 96.5 mL). To the reaction mixture was charged tri-o-tolylphosphine ((o-tol)3P, 506 mg) and trans-diaminedibromopalladium(II) ((NH3)2PdBr2> 454 mg). The batch was heated to 100 C and aged until completion. To the batch was charged 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 68.3 mL). The mixture was heated to 120C and aged for at least 6h. The batch was cooled to 45C, aq. Glycolic acid (56.8 mL, 70 wt %,) was slowly charged. Oxoalcohol VA was crystallized by slow addition of anti-solvent DI water at 55C. The crystalline product was dried at room temperature under vacuum with nitrogen sweep to yield oxoalcohol VA (110.7 g, 82% corrected yield from the vinyl alcohol IV. 1NMR (500MHz, CDCl3) delta 8.25 (m, 1H), 8.11 (d, J= 8.5 Hz, 1H), 8.08 (d, J= 1.5 Hz, 1H), 7.94 (m, 1H), 7.80 (m, 1H), 7.75 (d, J- 17.5 Hz, 1H), 7.72 (d, J= 5.0 Hz, 1H), 7.62 (d, J= 8.5 Hz, 1H), 7.49 (m, 1H), 7.46 (dd, J= 8.6, 2.0 Hz 1H), 7.43 (om, 1H), 7.42 (d, J= 16.3 Hz, 1H), 7.29 (dd, J= 7.6, 1.7 Hz, 1H), 7.24 (m, 1H), 7.19 (m, 1H), 3.49-3.42 (om, 4H), 2.47 (s, 1H), 1.73 (s, 6H). 13C NMR (125MHz, CDCl3) delta 199.7, 156.4, 148.6, 145.6, 139.8, 137.4, 136.8, 136.2, 135.6, 134.0, 131.6, 131.5, 129.6, 129.1, 128.7, 128.24, 128.21, 127.28, 127.26, 126.8, 126.0, 125.75, 125.69, 119.8, 73.8, 42.0, 32.2, 28.5. LC-MS (ESI+) m/z calculated C29H27C1N02 for 456.2 found 456.5 (M+H). | |
With tetrabutylammomium bromide; sodium acetate;palladium diacetate; In 1-methyl-pyrrolidin-2-one; toluene; at 120℃;Inert atmosphere; | 0.8 g (0.0037 mol) of palladium(II) acetate, 20.5 g (0.25 mol) of sodium acetate, 64.5 g (0.20 mol) of tetrabutylammonium bromide were placed under an argon atmosphere and 23.7 g (0.1 1 mol) of bromo-carbinol (III, X=Br) dissolved in 170 cm3 of toluene was added. The mixture was heated to 120C and then 32.2 g (0.10 mol) of chloroquinaldine-alcohol (II) dissolved in 70 cm3 of N-methyl-2-pirrolidone (NMP) was added. The mixture was stirred at 120 C until the reaction was complete. 100 cm3 of saturated NaHC03 solution, 100 cm3 of distilled water and 200 cm3 of ethyl acetate were then added. The mixture was stirred for 5 minutes. The layers were separated. The organic phase was washed three times with 200 cm3 of distilled water and with 200 cm3 of brine. The organic solution was dried over 30 g of sodium sulfate. The drying agent was filtered, washed with 200 cm3 of ethyl acetate and the filtrate was evaporated in vacuum. Yield: 54.7 g crude 1-{3-[(E)-2-(7-Chloro-quinolin-2-yl)-vinyl]-phenyl}-3-[2-(l-hydroxy-l- methyl-ethyl)-phenyl]-propan-l-one (IV) as a brown oil. A small amount of the product was purified by chromatography; the structure was checked by NMR spectroscopy: 1H NMR (DMSO-i/6) delta 1.57 (s, 6H, Me2C), 3.26-3.35 (m, 2H, CH2Ar), 3.40-3.48 (m, 2H, CH2CO), 5.04 (s, 1H, OH), 7.11-7.22 (m, 2H), 7.27-7.32 (m, 1H), 7.36-7.42 (m, 1H), 7.55-7.64 (m, 3H), 7.89-8.04 (m, 6H), 8.32-8.36 (m, 1H), 8.41 (d, 1H, J= 8.6 Hz) ppm.13C NMR (DMSO-i¾ delta 28.5 (CH2Ar), 2 31.8 ( e2C), 41.7 ( H2CO), 72.0 (Me2Q, 120.3, 125.5, 125.5, 125.6, 126.5, 126.8, 127.0, 127.2, 128.0, 129.3, 129.4, 129.7, 131.4, 131.5, 134.1, 134.4, 136.6, 136.6, 137.3, 139.8, 146.8, 148.0, 156.6, 199.6 (CO) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trans dibromo diammine palladium (II); N-Methyldicyclohexylamine; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 100℃;Inert atmosphere; | A flask under nitrogen was charged with vinyl alcohol IV (97 g), bromo alcohol IIA (81g ), DMF (380 mL) and N,N-dicyclohexylmethylamine (Cy2NMe, 96.5 mL). To the reaction mixture was charged tri-o-tolylphosphine ((o-tol)3P, 506 mg) and trans-diaminedibromopalladium(II) ((NH3)2PdBr2> 454 mg). The batch was heated to 100 C and aged until completion. To the batch was charged 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 68.3 mL). The mixture was heated to 120C and aged for at least 6h. The batch was cooled to 45C, aq. Glycolic acid (56.8 mL, 70 wt %,) was slowly charged. Oxoalcohol VA was crystallized by slow addition of anti-solvent DI water at 55C. The crystalline product was dried at room temperature under vacuum with nitrogen sweep to yield oxoalcohol VA (110.7 g, 82% corrected yield from the vinyl alcohol IV. 1NMR (500MHz, CDCl3) delta 8.25 (m, 1H), 8.11 (d, J= 8.5 Hz, 1H), 8.08 (d, J= 1.5 Hz, 1H), 7.94 (m, 1H), 7.80 (m, 1H), 7.75 (d, J- 17.5 Hz, 1H), 7.72 (d, J= 5.0 Hz, 1H), 7.62 (d, J= 8.5 Hz, 1H), 7.49 (m, 1H), 7.46 (dd, J= 8.6, 2.0 Hz 1H), 7.43 (om, 1H), 7.42 (d, J= 16.3 Hz, 1H), 7.29 (dd, J= 7.6, 1.7 Hz, 1H), 7.24 (m, 1H), 7.19 (m, 1H), 3.49-3.42 (om, 4H), 2.47 (s, 1H), 1.73 (s, 6H). 13C NMR (125MHz, CDCl3) delta 199.7, 156.4, 148.6, 145.6, 139.8, 137.4, 136.8, 136.2, 135.6, 134.0, 131.6, 131.5, 129.6, 129.1, 128.7, 128.24, 128.21, 127.28, 127.26, 126.8, 126.0, 125.75, 125.69, 119.8, 73.8, 42.0, 32.2, 28.5. LC-MS (ESI+) m/z calculated C29H27C1N02 for 456.2 found 456.5 (M+H). |
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