Structure of 2-Acetyl-6-bromopyridine
CAS No.: 49669-13-8
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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. : | 49669-13-8 |
Formula : | C7H6BrNO |
M.W : | 200.03 |
SMILES Code : | C(C)(=O)C1=NC(=CC=C1)Br |
MDL No. : | MFCD00272200 |
InChI Key : | RUJTWTUYVOEEFW-UHFFFAOYSA-N |
Pubchem ID : | 11298578 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 42.13 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.96 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.98 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.89 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.33 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.83 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.65 |
Solubility | 0.449 mg/ml ; 0.00224 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.14 |
Solubility | 1.44 mg/ml ; 0.00722 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.22 |
Solubility | 0.121 mg/ml ; 0.000605 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 |
-6.18 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) |
1.65 |
* 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 |
---|---|---|
98% | Preparation 31 Synthesis of 2-(6-bromo-pyridin-2-yl)-propan-2-ol Add a solution of methyl magnesium bromide (3.0 M, 9.7 mL, 29.09 mmol) in tetrahydrofuran dropwise over 20 min to a cooled solution of 1-(6-bromo-pyridin-2-yl)-ethanone (5 g, 24.25 mmol) in anhydrous tetrahydrofuran (48.5 mL) at 0 C. Upon completion of the reaction, add water (exothermic), dilute with ethyl acetate (50 mL) and separate the layers. Extract the aqueous layer once with ethyl acetate (50 mL). Dry the combined organic layers over sodium sulfate, filter and concentrate to give the title compound as a pale yellow liquid (5.69 g, 98%) that is used without further purification. 1H NMR (CDCl3) delta 1.55 (s, 6H), 4.07 (s, 1H), 6.59 (t, 1H), 7.37 (t, 2H), 7.55 (t, 1H). | |
98% | In tetrahydrofuran; at 20℃; for 16h; | To a solution of l-(6-bromo-pyridin-2-yl)-ethanone (4.0 g, 20 mmol) in anhydrous THF (50 mL) at 0 C was added a solution of methyl magnesium bromide (3.0 M, 8.0 mL, 24 mmol, 1.2 eq) in THF dropwise over 20 min. The mixture was stirred at rt for 16 h, quenched with H20 (30 mL) and extracted by EA (4 x 30 mL). The organic phase was washed with brine (30 mL) and dried over Na2S04. After filtration and concentration, the residue was directly used for next step without further purification. 4.2 g, Y: 98%. ESI-MS (M+H)+: 216. |
A solution of l-(6~bromorhoyridin-2-yl)ethanone (5 g, 25.0 mmol) in diethyl ether (77 ml) at 00C was treated with methyl magnesium bromide (8.33 ml, 25.0 mmol). After 3 hours, water was added to quench excess methyl magnesium bromide, and then concentrated aqueous hydrogen chloride solution was added until two layers were obtained. The layers were separated and the aqueous layer was extracted with diethyl ether (3 x 50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to yield the title compound. LRMS (APCI) calc'd for C8H1 jBrNO [M+H]+: 216, Found: 216. |
In diethyl ether; at 0℃; for 3h; | A solution of l-(6-bromopyridin-2-yl)ethanone (5 g, 25.0 mmol) in diethyl ether (77 mL) at 0C was treated with methyl magnesium bromide (8.33 mL, 25.0 mmol). After 3 hours, water was added to quench the excess methyl magnesium bromide, and then concentrated aqueous hydrogen chloride solution was added until two layers were obtained. The layers were separated and the aqueous layer was extracted with diethyl ether (3 x 50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to yield the title compound.Calc'd for C8HnBrNO [M+H]+: 216, Found: 216. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 16h;Reflux; Inert atmosphere; | The colorless oily liquid of Preparation 1 (0.68 g, 2.5 mmol), 6-acetyl-2-bromopyridine (0.50 g, 2.5 mmol) and tetrakis(triphenylphosphine)palladium(Pd(PPh3)4, 144 mg, 0.13 mmol) were added in a 100 ml single neck bottle followed by adding THF (25 ml) and a potassium carbonate solution (potassium carbonate (0.69 g) in deionized water (5 ml)) to obtain a mixture. The mixture was heated under reflux for 16 hours under a nitrogen gas atmosphere. After the reaction was finished, the mixture was cooled to room temperature, followed by removing solvent by virtue of reduced pressure distillation to obtain a distilled mixture. Then, the distilled mixture was added with dichloromethane and water for extraction. The dichloromethane layer was collected and added with magnesium sulfate to remove water. The dichloromethane layer was then filtrated and the filtrate was collected. Next, the filtrate was concentrated by means of reduced pressure distillation to obtain a yellow crude product. The resultant yellow crude product was subjected to column chromatography, in which a mixture of ethyl acetate and hexane(ethyl acetate: hexane=1:8) was used as an eluent. An eluate was collected followed by removing the eluent using a rotary evaporator. A white solid product was obtained (446 mg, 1.7 mmol, 67% yield). The spectrum analysis for the white solid product is: 1H NMR (400 MHz, CDCl3, 298K), delta(ppm): 8.34 (s, 1H), 8.27 (d, JHH=8.0 Hz, 1H), 8.02 (dd, JHH=6.8 Hz, 2.0 Hz, 1H), 7.98?7.90 (m, 2H), 7.70 (d, JHH=8.0 Hz, 1H), 7.63 (t, JHH=8.0 Hz, 1H), 2.82 (s, 3H). |
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