Structure of 3-Amino-2-cyclohexen-1-one
CAS No.: 5220-49-5
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CAS No. : | 5220-49-5 |
Formula : | C6H9NO |
M.W : | 111.14 |
SMILES Code : | NC(CCC1)=CC1=O |
MDL No. : | MFCD00013783 |
InChI Key : | ZZMRPOAHZITKBV-UHFFFAOYSA-N |
Pubchem ID : | 78892 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 31.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.09 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.12 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.07 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.58 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.04 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.96 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.51 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.48 |
Solubility | 36.4 mg/ml ; 0.327 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.38 |
Solubility | 46.0 mg/ml ; 0.414 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.77 |
Solubility | 19.0 mg/ml ; 0.171 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 |
-7.03 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) |
2.28 |
* 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 |
---|---|---|
7% | toluene-4-sulfonic acid; In N,N-dimethyl-formamide; for 16h;Heating / reflux; | A mixture of 3-aminocyclohex-2-enone (100 mmol), 1 ,1 , 3,3- tetraethoxypropane (1 10 mmol), and 4-methylbenzenesulfonic acid (2.91 mmol) is diluted with lambda/,lambda/-dimethylformamide (40 ml_) and the reaction mixture is heated at reflux for 16 h. The reaction mixture is allowed to cool to rt, neutralized with sodium bicarbonate, diluted with water (400 ml_), and is extracted with ethyl acetate (3 x 100 ml_). The combined organic layers are dried (sodium sulfate) and concentrated. The residue is purified by chromatography (10/1 petroleum ether/ethyl acetate) to provide 5,6,7,8-tetrahydroquinolin-5-one in 7% yield as a colorless oil. |
toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 140℃; for 18h; | To a solution of 10.12 g (0.14 mmol) 3-aminocyclohex-2-en-l-one and 22 mL 1,1,3,3- tetraethoxypropane in 40 mL dry DMF under nitrogen atmosphere was added 0.5 g (cat.) p- toluenesulfonic acid. The reaction mixture was heated at 140 0C for 18 hr. The volatiles were removed under vacuum and the residue distilled under vacuum to give an oil. This material was further purified by column chromatography on silica gel eluting with hexanes/EtOAc (3/1) then EtOAc (100%) afford 1.75 g of the title compound. LC-MS: (MH)+: 148.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium chloride; In N-methyl-acetamide; | PREPARATION D To a mechanically-stirred slurry consisting of 60 g. of lithium chloride in 350 ml. of anhydrous dimethylformamide at 40 C., there were added 88.9 g. (0.80 mole) of 3-amino-2-cyclohexene-1-one (the product of Preparation C). When all this material had dissolved, the temperature was increased to 60 C. and all of the 1,2-dichloro-1-propen-3-al obtained in Preparation B (i.e., the product of Preparation B) was added in one portion. This resulted in a mild exotherm accompanied by vigorous bubbling. After allowing the reaction mixture to stand at 90 C. for a period of one hour, the reaction flask and its contents were cooled to 25 C. and the contents were poured over 400 ml. of water. The resulting slurry was then extracted with twelve-500 ml. portions of hexanes, which were subsequently combined and then dried over anhydrous magnesium sulfate. After removal of the drying agent by means of filtration and the solvent by means of evaporation under reduced pressure, there were eventually obtained 51.62 g. (28%) of pure 3-chloro-5,6,7,8-tetrahydro-5-quinolone in the form of a yellow solid melting at 88-94 C.; 1 H-NMR (300 MHz, DMSO-d6)delta2.10 (m, 2H), 2.65 (t, 2H), 3.05 (t, 2H), 8.08 (s, 1H), 8.70 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30.2 g (54.2%) | In N,N-dimethyl-formamide; | EXAMPLE 1 7,8-Dihydro-5(6H)-quinolinone The procedure of Rimek and Zymalkowski (Arch. Pharm. 1961, 294, 759-765) was followed. Over a period of 1 hour, 40.9 g (0.757 mol) of freshly-distilled propiolaldehyde was added dropwise to a solution of 42.1 g (0.379 mol) of 3-amino-2-cyclohexenone in 1.5 1 of N,N-dimethylformamide (DMF). The solution was stirred at room temperature for 12 hours. The DMF was evaporated at reduced pressure. Vacuum distillation (bp 60-65 C. at 0.025-0.050 mmHg) of the resultant black tars gave 30.2 g (54.2%) of 7,8-dihydro-5(6H)-quinolinone as a colorless liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 983-((6-Aminopyridin-2-yl)ethynyl)-7,8-dihydroquinolin-5(6H)-one[00286] A mixture of cyclohexane-1 ,3-dione (30.0 g, 0.27 mol), ammonium acetate (44.49 g, 0.54 mol), and acetic acid (1 mL) in benzene (300 mL) is stirred at reflux for 7 h using a Dean-Stark trap, cooled down to r.t., concentrated at reduced pressure, and diluted with EtOH. The mixture is neutralized by means of NaHC03. The formed solid is collected by filtration, and the filtrate is concentrated in vacuo. The obtained residue is dissolved in dioxane, and the residual solids are filtered. A precipitate is formed, which is collected by filtration and dried at 50 C to give 3-aminocyclohex-2-enone (intermediate I) (6.77 g, 23%) as yellow solid.[00287]A mixture of 2-bromomalonaldehyde (7.51 g, 49.75 mmol) and thionyl chloride (3.65 mL, 49.75 mmol) in anhydrous DCM (35 mL) is stirred at reflux for 9 h, cooled down to r.t. and concentrated at reduced pressure to give 2-bromo-3- chloroacrylaldehyde (intermediate II) (6.55 g, 88%) as red oil, which is used in the next step without additional purification.[00288] Intermediate I (3.90 g, 35.10 mmol) is added to a solution of LiCI (2.60 g, 61 .45 mmol) in DMF (60 mL) at 40 C, and the resulting solution is stirred at 50 C for 5 min. Intermediate II (6.550 g, 43.91 mmol) is added, and the reaction mixture is stirred at 90 C for 1.5 h, cooled down to r.t., poured into water and extracted with EtOAc. The organic phase is concentrated at reduced pressure. The obtained residue is purified by column chromatography (silica gel, EtOAc/hexane) to give a mixture of 3-bromo-7,8- dihydroquinolin-5(6/-/)-one and 3-chloro-7,8-dihydroquinolin-5(6/-/)-one (4.940 g) as yellowish oil (ratio approx. 1 : 1 according to LCMS). [00289]According to General Procedure 1 , the 1 : 1 mixture of halogenated 7,8- dihydroquinolin-5(6/-/)-ones (500 mg, approx. 2.45 mmol) is reacted with 6- ethynylpyridin-2-amine (292 mg, 2.45 mmol) in the presence of PdCI2[PPh3]2 (52 mg, 0.07 mmol), P(f-Bu)3 (0.061 mL, 0.25 mmol), and TEA (4 mL) in acetonitrile (4 mL) at 100 C for 2 h. The crude product is purified by column chromatography (silica gel, EtOAc/hexane) to provide the title compound (90 mg, 14%).1H NMR (De-DMSO), deltaEta, 2.05-2.15 (m, 2H), 2.67 (t, 2H), 3.09 (t, 2H), 6.1 1 (br s, 2H), 6.48 (d, 1 H), 6.80 (d, 1 H), 7.40 (dd, 1 H), 8.18 (s, 1 H), 8.83 (s, 1 H).LC/MS (M+H)+ = 264 |
Tags: 5220-49-5 synthesis path| 5220-49-5 SDS| 5220-49-5 COA| 5220-49-5 purity| 5220-49-5 application| 5220-49-5 NMR| 5220-49-5 COA| 5220-49-5 structure
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