Structure of 6919-61-5
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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. : | 6919-61-5 |
Formula : | C9H11NO2 |
M.W : | 165.19 |
SMILES Code : | O=C(N(OC)C)C1=CC=CC=C1 |
MDL No. : | MFCD00075320 |
InChI Key : | UKERDACREYXSIV-UHFFFAOYSA-N |
Pubchem ID : | 569575 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.42 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.54 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.13 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.67 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.78 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.46 |
Solubility | 5.75 mg/ml ; 0.0348 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.87 |
Solubility | 22.4 mg/ml ; 0.136 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.19 |
Solubility | 1.07 mg/ml ; 0.00647 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 |
-6.83 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 |
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) |
1.36 |
* 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 |
---|---|---|
Reference Example 30; (2,6-Difluoropyridin-3-yl)(phenyl)methanoneTo a solution of 2,6-difluoropyridine (1.0 g, manufactured by Tokyo Chemical Industry Co., Ltd.) in tetrahydrofuran (40 mL, manufactured by Kanto Chemical Co., Inc.), lithium diisopropylamide (23% solution in tetrahydrofuran/ethylbenzene/heptane, 5.79 mL, manufactured by Sigma-Aldrich Corp.) was added dropwise at -78 C., and the mixture was stirred for 30 minutes. Subsequently, N-methoxy-N-methylbenzamide (1.46 mL, manufactured by Sigma-Aldrich Corp.) was further added at the same temperature, and while the temperature was gradually raised to room temperature, the mixture was stirred overnight. A saturated aqueous solution of ammonium chloride (30 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (3×30 mL), washed with brine (30 mL), and dried (MgSO4). The solvent was then evaporated, to give 1.90 g of the title compound. LC-MS: HPLC retention time 1.63 minutes, m/z (M-F+OMe) 232, condition C-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | -Phenyl-2-(pyridin-4-yl)ethanone (2): Lithium diisopropyl amide (16.9 mL, 1.5 M in cyclohexane, 25.4 mmol) was added to THF (40 mL) at -78 0C. A solution of 4-picoline (2.50 mL, 25.4 mmol) in THF (30.0 mL) was added dropwise to the LDA solution. The dry ice bath was removed. The reaction mixture was stirred at 0 C for 30 minutes, and cooled down to -78 "C. A solution of N-methoxy-N- methylbenzamide (1) (5.00 g, 29.6 mmol) in THF (20.0 mL) was added dropwise. The reaction mixture was warmed to room temperature and stirred overnight. The mixture was quenched with water, and extracted with ethyl acetate (3x). The pooled organic layer was dried over magnesium sulfate. The mixture was filtered, and the solvent was removed under vacuum to give the crude product. The crude material was triturated with hot hexane, and filtered to give l-phenyl-2-(pyridin-4-yl)ethanone (2) as a yellow solid (3.53 g, 17.9 mmol, 70% yield). | |
70% | l-Phenyl-2-(pyridin-4-yl)ethanone (2): Lithium diisopropyl amide (16.9 mL, 1.5 M in cyclohexane, 25.4 mmol) was added to THF (40 mL) at -78 0C. A solution of 4- picoline (2.50 mL, 25.4 mmol) in THF (30.0 mL) was added dropwise to the LDA solution. The dry ice bath was removed. The reaction mixture was stirred at 0 0C for 30 minutes, and cooled down to -78 0C. A solution of N-methoxy-N-methylbenzamide (1) (5.00 g, 29.6 mmol) in THF (20.0 mL) was added dropwise. The reaction mixture was warmed to room temperature and stirred overnight. The mixture was quenched with water, and extracted with ethyl acetate (3x). The pooled organic layer was dried over magnesium sulfate. The mixture was filtered, and the solvent was removed under vacuum to give the crude product. The crude material was triturated with hot hexane, and filtered to give l-phenyl-2-(pyridin-4-yl)ethanone (2) as a yellow solid (3.53 g, 17.9 mmol, 70% yield). | |
To a stirred solution of lithium diisopropylamide (1.5 eq) in THF at -78 C. a solution of 4-picoline (1 eq) in THF is added slowly. After 15 min, a solution of N-methoxy-N-methylbenzamide (1.2 eq) in THF is added. The reaction mixture is allowed to warm to ambient temperature. The formation of product is monitored by HPLC. The reaction mixture is poured into a saturated aqueous sodium bicarbonate solution, then extracted with ethylacetate. The organic phase is washed with brine, dried over anhydrous magnesium sulphate and evaporated under reduced pressure to give the crude product. The crude product is then purified by flash column chromatography (25-100% EtOAc-hexane) to give the product ketone 2. Purity >90%, ESI m/z 198.18 (MH+). |
THF in a round bottom flask was cooled (-78 C), lithium diisopropylamide added to the flask with stirring under argon atmosphere, and a solution of 4-picoline (in THF) carefully added to the cooled flask under constant stirring. After one hour, a solution ofN-methoxy-N-methylbenzamide (in THF) was added over a period of 30 min. Formation of the product was monitored by HPLC and TLC. The reaction mixture was warmed to ambient temperature, during which time the color changed from light yellow to orange, and the reaction quenched with crushed ice addition. THF was removed in vacuo, the reaction mixture was treated with saturated sodium bicarbonate solution, and repeat extraction with ethyl acetate was done in a separately funnel The combined organic extracts were treated with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield an oily mixture. The crude mixture was purified by column chromatography on silica gel (200-400 mesh) with product elution using ethyl acetate: hexane (1 :4 v/v). The product, ketone 2-1, was obtained as a bright yellow solid in 69% (gravimetric) yield, 90% purity by HPLC and a mass (ESI) oim/z (MeOH) = 198.18 (MH ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | To a solution of 5-bromo-1 ,2-dimethyl-1H-imidazole (10.0 g, 57.1 mmol) in dichloromethane (50 ml_) was added dropwise ethylmagnesium bromide (3 M in Et2O, 19.0 ml_, 57.0 mmol). After stirring at room temperature for 30 min, the reaction mixture was cooled down to 0C with an <n="114"/>ice-brine bath and N-Methoxy-N-methyl-benzamide (8.70 ml_, 57.1 mmol) was added dropwise. The mixture was stirred for 7.5h at room temperature. The mixture was worked-up by addition of water (100 ml_), then acidified with aq. HCI (1 M) until pH = 7. After extraction with dichloromethane (2 x 75 ml_), the organic layers were washed with water (2 x 100 ml_) then dried over MgSO4 and concentrated in vacuo. Purification of the residue on silica gel afforded (1 ,2-dimethyl-1H-imidazol-5-yl)(phenyl)methanone [8.41 g, yield 44% ; HPLC/MS : m/z = 201 (M+H) ; logP(HcooH) = 0.56]. |
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