Structure of 1798-83-0
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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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CAS No. : | 1798-83-0 |
Formula : | C11H15Cl2NO |
M.W : | 248.15 |
SMILES Code : | O=C(C1=CC=C(Cl)C=C1)CCN(C)C.[H]Cl |
MDL No. : | MFCD00084951 |
Boiling Point : | No data available |
InChI Key : | MQURAWQCJQTMJM-UHFFFAOYSA-N |
Pubchem ID : | 200370 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.36 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 65.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.31 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.01 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.28 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.59 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.31 |
Solubility | 0.122 mg/ml ; 0.000493 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.1 |
Solubility | 0.197 mg/ml ; 0.000792 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.89 |
Solubility | 0.032 mg/ml ; 0.000129 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 |
-5.68 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 |
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) |
1.35 |
* 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 |
---|---|---|
In water; for 5h;Reflux; | General procedure: The appropriate acetophenone 1a-d (200 mmol), dimethylamine hydrochloride (270 mmol) andparaformaldehyde (90 mmol) were heated to reflux in absolute ethanol (35 mL) in the presence ofcatalytic amount of concentrated hydrochloric acid (0.5 mL). Reflux of the reaction mixture was continuedunder stirring for two hours, cooled and acetone (200 mL) was added. The formed Mannich basehydrochlorides 2a-d were precipitated, filtered off and dried. Subsequently, compounds 2a-d (100 mmol)were dissolved in water (100 mL) and imidazole (200 mmol) was added. The reaction mixture washeated to reflux for five hours, cooled and the precipitated solids were collected by filtration to giveketones 3a-d which were pure enough to be used in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11 g | With sodium acetate; In ethanol; for 12h;Reflux; | 15 g of N, N-dimethyl-3-oxo-3,4-chlorophenyl-propyl-1-ammonium chloride are addedInto 270 ml of ethanol,Then add 40g of anhydrous sodium acetate and 19g1,2,3-triazole,Heated to reflux for 12 hours,Concentrate, add water and ethyl acetate,Extract the liquid, collect the organic phase,Dry, concentrate,11 g of 1, 4-chlorophenyl-3- (1H-1,2,4-triazol-1-yl) propan-1-one was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.2% | General procedure: A reaction mixture of the aralkyl-ketone (IV) (0.1 mol), the hydrochloride of the corresponding amine (VIII) (0.11 mol) and the polyformaldehyde (0.13 mol) dissolved in 95% ethanol (20 mL) is added with wt % concentrated HCl (0.2 mL) and refluxed for 5 h. TLC (dichloromethane: methanol=20:1) indicates a complete consumption of the starting material (IV). The solvent is concentrated down till dry. To the residue, dichloromethane (100 mL) and saturated NaHCO3 solution (40 mL) are added, followed by a 20-min stirring. The organic phase is separated and washed with 5 wt % dilute HCl solution (30 mL). After dried over anhydrous MgSO4, the organic phase is filtered and then concentrated to give the crude product which is then dissolved in ethyl acetate (30 mL) and formed a hydrochloride by adding hydrochloric acid alcohol to the mixture. The intermediate (III) is thus obtained with a yield of 70-90% based on the intermediate (IV). | |
62% | With hydrogenchloride; In ethanol; water; at 80 - 90℃; for 30h; | To a solution of 4’-chloroacetophenone (10 g, 65 mmol) in absolute EtOH (50 ml_) at room temperature were added paraformaldehyde (1.94 g, 64 mol), N,N- dimethylamine hydrochloride (5.27 g, 64.68 mmol) and cone. HCI (2 ml_). The resulting reaction mixture was stirred at between 80-90 C for 30 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by column chromatography with silica gel (60-120 mesh) eluting with 2% EtOAc/hexane) and trituration with Et20 (100 ml_) to afford the title compound (10 g, 40 mmol, 62 %). |
59.2% | With sulfuric acid; In acetonitrile; for 9h;Reflux; Inert atmosphere; | General procedure: To a solution of acetophenone (1 eq.), paraformaldehyde (1.3 eq.) and N,N-dimethylamine hydrochloride (1.3 eq) in acetonitrile (35 mL) was added sulfuric acid (1 mL) dropwise. The reaction mixture was stirred at reflux temperature for 9 h. After the solution was cooled to room temperature, the reaction mixture was poured into acetone (50 mL). The formed precipitate was filtered, washed with acetone, and dried over by vacuum. |
With hydrogenchloride; In ethanol; water; for 5h;Heating / reflux; | 1 -(4-Chloro-phenyl)-3-dimethylamino-propan-1 -one hydrochlorideTo EtOH (80 mL), p-chloroacetophenone (77.3 g, 0.50 mol), dimethylamine hydrochloride (52.7 g, 0.65 mol), paraformaldehyde (19.8 g, 0.66 mol) and concentrated aqueous HCI (1 mL) were added and the mixture was refluxed for 5 h. The mixture was cooled to 400C, acetone (400 mL) was added, and under stirring the mixture was cooled further to 20C. The precipitate was filtered, washed with acetone and PA, and air dried to obtain 69.5 g of product which was used without further purification in the subsequent step. | |
With hydrogenchloride; In ethanol; for 2h;Reflux; | General procedure: The appropriate acetophenone 1a-d (200 mmol), dimethylamine hydrochloride (270 mmol) andparaformaldehyde (90 mmol) were heated to reflux in absolute ethanol (35 mL) in the presence ofcatalytic amount of concentrated hydrochloric acid (0.5 mL). Reflux of the reaction mixture was continuedunder stirring for two hours, cooled and acetone (200 mL) was added. The formed Mannich basehydrochlorides 2a-d were precipitated, filtered off and dried. Subsequently, compounds 2a-d (100 mmol)were dissolved in water (100 mL) and imidazole (200 mmol) was added. The reaction mixture washeated to reflux for five hours, cooled and the precipitated solids were collected by filtration to giveketones 3a-d which were pure enough to be used in the next step. |