Structure of 2732-28-7
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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. : | 2732-28-7 |
Formula : | C8H9NO |
M.W : | 135.16 |
SMILES Code : | C(C)(=O)C1=CC(=NC=C1)C |
MDL No. : | MFCD07375079 |
InChI Key : | NIGBUKPEJHINOG-UHFFFAOYSA-N |
Pubchem ID : | 20705014 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.4 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.96 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.78 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.46 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.55 |
Solubility | 3.83 mg/ml ; 0.0284 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.99 |
Solubility | 13.8 mg/ml ; 0.102 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.72 |
Solubility | 0.26 mg/ml ; 0.00192 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) |
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) |
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 |
-6.57 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) |
1.12 |
* 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 |
---|---|---|
56.4% | at -78 - 20℃; for 1 h; Inert atmosphere | To a stirred solution of N-methoxy-N,2-dimethylisonicotinamide (266c) (26 g,144.28Immol) in THF (520 rnL) was added MeLi (6.342 g, 288.562 mmoi, 1 M solution inTHF) under nitrogen atmosphere at -78°C. The reaction mixture was warmed to room temperature over a period of 1 h, quenched with saturated NH4CI solution at 0°C. The resulting reaction mixture was extracted with ethyl acetate and the organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated. Theresidue obtained was purified by column chromatography to afford I -(2-methylpyridin-4-yl)ethanone (266d) (11 g, 56.4percent yield) as a reddish thick liquid; ‘H NMR (CDCI3) 3 8.6 1-8.59 (d, 1H), 7.51-7.45 (d, IH), 7.45-7.44 (m, lH), 2.56(s, 3H), 2.53 (s, 3H); MS (ES+)136. l(M+I). |
56.4% | at -78 - 20℃; for 1 h; Inert atmosphere | Step-3 : Preparation of l-(2-methylpyridin-4-yl)ethanone (46d) To a stirred solution of N-methoxy-N,2-dimethylisonicotinamide (46c) (26 g, 144.28 lmmol) in THF (520 mL) was added MeLi (6.342 g, 288.562 mmol, 1 M solution in THF) under nitrogen atmosphere at -78°C. The reaction mixture was warmed to room temperature over a period of 1 h, quenched with saturated H4C1 solution at 0°C. The resulting reaction mixture was extracted with ethyl acetate and the organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue obtained was purified by column chromatography to afford l-(2-methylpyridin-4-yl)ethanone (46d) (11 g, 56.4percent yield) as a reddish thick liquid; 1H MR (CDC13) δ 8.61-8.59 (d, 1H), 7.51-7.45 (d, 1H), 7.45-7.44 (m, 1H), 4.05-4.02 (s, 3H); MS (ES+) 136.1(M+1). |
51% | Stage #1: at -78 - 20℃; for 1.5 h; Inert atmosphere Stage #2: With ammonium chloride In tetrahydrofuran |
Methyl lithium (3M, 1.7 mL, 3.48mmol) was added to a solution of N-methoxy-N2- dimethylisonicotinamide (314 mg, 1.74mmol) in dry THF (4 mL) at -78 °C under nitrogen protection. The mixture was stirred at -78 °C and slowly warm up to rt for 1.5h. After completion, 10 mL of NH4C1 solution (saturated) was added to the mixture, and it was extracted with EtOAc (10 mLx3). The combined organic layers were washed with brine (20 mL), dried over Na2S04, and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (CH2Cl2/MeOH=50/l) to obtain title compound (120mg, yield: 51percent). LCMS-AOIO: 136.1 [M+H]+; Rt = 0.585 min |
51% | at -78 - 20℃; for 1.5 h; Inert atmosphere | (b) I -(2-methyipyridin-4-yl)ethanone: Methyl lithium (3M, 1.7 mL, 3.48inniol) was added to a solution of W-methoxy-X, 2-dimethyiisonieotinamide (314 ing, I .74mmol) in dry THE (4 mL) at -78 °C under nitrogen protection. The mixture was stirred at -78 °C and slowly warm up to it for l.5h. After completion, 10 niL of NI-LCI solution (saturated) was added to the mixture, and it was extracted with EtOAc (10 mLx3). The combined organic layers were washed with brine (20mL), dried over Na2SO4, and filtered. The filtrate was eoneeitmated, and the residue was purified by silica gel column chromatography (CH2C12/MeOH=50/i) to obtain title compound (120mg, yield: 51percent). LCMS-A0i0: 136.1 [M+H] R = 0.585 mm |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | Stage #1: at 0℃; Heating; Reflux Stage #2: With hydrogenchloride In tetrahydrofuran; hexane; water at 20℃; |
[0352] l-(2-Methyl-4-pyridinyl)ethanone (143). A solution of MeMgBr (3 M in hexanes, 6.0 mL, 17.9 mmol) was added slowly to a stirred solution of nitrile 142 (1.76 g, 14.9 mmol) in dry THF (100 mL) at 0 0C and the mixture was stirred at reflux temperature for 16 h. The mixture was cooled to 20 0C and the reaction quenched with 6 M HCl (30 mL). The aqueous fraction was separated and the organic fraction extracted with 1 M HCl (30 mL). The combined acidic fraction was stirred at 80 0C for 1 h, cooled to 0 0C and made basic with cNH3 solution. The mixture was extracted with CHCl3 (3 x 50 mL), the combined organic fraction was washed with brine (50 mL), dried and the solvent evaporated. The residue was purified by column chromatography, eluting with 50percent EtO Ac/pet, ether, to give ketone 143 (0.50 g, 25percent) as an oil: 1H NMR (CDCl3) δ 8.68 (d, J= 5.1 Hz, 1 H, H-6'), 7.59 (br s, 1 H, H-3'), 7.52 (d, J= 5.1 Hz, 1 H, H-5'), 2.65 (s, 3 H, H-2), 2.61 (s, 3 H, CH3); MS m/z 136.5 (MH+, 100percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With tetrakis(triphenylphosphine) palladium(0) In toluene at 80℃; Inert atmosphere | To a solution of 4-bromo-2-methylpyridine (10.0 g, 58 mmol) in toluene (100 mL) was added tributyl(l-ethoxyvinyl)stannane (39.7 g, 110 mmol) and Pd(PPh3)4 (5.8 g, 5 mmol). The mixture was stirred at 80 °C under a nitrogen atmosphere overnight. IM HCl was added at 0 °C until the pH of the mixture was adjusted to 1-2. The mixture was stirred for 0.5 h. The pH was adjusted to 6-7 by adding IM NaOH. The mixture was extracted with ethyl acetate (150 mL*3). The organics layer was washed with brine and dried over sodium sulfate. Concentration and purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 30/1-4/1) afforded l-(2-methylpyridin-4-yl)ethanone as light yellow solid (3.0 g, 44percent). |
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