Structure of 103426-20-6
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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. : | 103426-20-6 |
Formula : | C8H7ClO |
M.W : | 154.59 |
SMILES Code : | O=CC1=CC(C)=CC(Cl)=C1 |
MDL No. : | MFCD11553565 |
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 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.81 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.85 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.82 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.46 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.37 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.52 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.95 |
Solubility | 0.172 mg/ml ; 0.00111 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.84 |
Solubility | 0.226 mg/ml ; 0.00146 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.33 |
Solubility | 0.0718 mg/ml ; 0.000465 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 |
-5.24 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 |
2.0 |
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) |
1.05 |
* 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 |
---|---|---|
With hydrogenchloride; sodium hydroxide; N-Bromosuccinimide; potassium tert-butylate; silver nitrate; dibenzoyl peroxide; In tetrachloromethane; water; | 3-Chloro-5-methylbenzoic acid A well stirred mixture of N-bromosuccinimide (32.5 g), 5-chloro-m-xylene (25.6 g) and carbon tetrachloride (500 ml) is refluxed for 8 hours. The solution is well illuminated and every 2 hours small quantities of benzoyl peroxide are added. The cooled mixture is filtered and the solvent evaporated to give an oil consisting of a mixture of 3-chloro-5-methylbenzyl bromide and 5-chloro-m-xylene in a ratio of about 2:1 (34.5 g). The above mixture is added to a stirred mixture of potassium tert-butoxide (14 g), 2-nitropropane (11 g) and dimethylsulphoxide (100 ml) and the mixture is stirred overnight at room temperature. Water (500 ml) is added and the separated oil extracted with ether. Evaporation of the dried ether solution yields an oil consisting of a mixture of <strong>[103426-20-6]3-chloro-5-methyl-benzaldehyde</strong> and 5-chloro-m-xylene (approximately 1:1) (18.5 g). The above mixture is slowly added over a 15 minute period to a stirred suspension of moist silver oxide [prepared from silver nitrate (24 g) and an aqueous solution of sodium hydroxide (5.7 g)] in a solution of sodium hydroxide (5.7 g) in water (50 ml). The stirred mixture is refluxed for 30 minutes, cooled, filtered and the filtrate extracted with ether. Acidification of the aqueous layer with 2N HCl yields a precipitate which is filtered and recrystallized from aqueous methanol to yield 3-chloro-5-methylbenzoic acid, 174-175 C. (9.4 g). | |
With hydrogenchloride; sodium hydroxide; N-Bromosuccinimide; potassium tert-butylate; silver nitrate; dibenzoyl peroxide; In tetrachloromethane; water; | 3-Chloro-5-methylbenzoic acid A well stirred mixture of N-bromosuccinimide (32.5 g), 5-chloro-m-xylene (25.6 g) and carbon tetrachloride (500 ml) is reflexed for 8 hours. The solution is well illuminated and every 2 hours small quantities of benzoyl peroxide are added. The cooled mixture is filtered and the solvent evaporated to give an oil consisting of a mixture of 3-chloro-5-methyl-benzyl bromide and 5-chloro-m-xylene in a ratio of about 2:1 (34.5 g). The above mixture is added to a stirred mixture of potassium tert-butoxide (14 g), 2-nitropropane (11 g) and dimethylsulphoxide (100 ml) and the mixture is stirred overnight at room temperature. Water (500 ml) is added and the separated oil extracted with ether. Evaporation of the dried ether solution yields an oil consisting of a mixture of <strong>[103426-20-6]3-chloro-5-methyl-benzaldehyde</strong> and 5-chloro-m-xylene (approximately 1:1) (18.5 g). The above mixture is slowly added over a 15 minute period to a stirred suspension of moist silver oxide [prepared from silver nitrate (24 g) and an aqueous solution of sodium hydroxide (5.7 g)] in a solution of sodium hydroxide (5.7 g) in water (50 ml). The stirred mixture is refluxed for 30 minutes, cooled, filtered and the filtrate extracted with ether. Acidification of the aqueous layer with 2N HCl yields a precipitate which is filtered and recrystallized from aqueous methanol to yield 3-chloro-5-methylbenzoic acid, 174-5 C. (9.4 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In chloroform; N,N-dimethyl-formamide; | EXAMPLE 12 3-Chloro-5-methylphenyl-(trichloromethyl)carbinol A cold solution (-10 C.) of <strong>[103426-20-6]3-chloro-5-methylbenzaldehyde</strong> (19.5 g) and chloroform (15.6 ml) in 76 ml of DMF was treated dropwise with a 5M methanolic KOH solution (17.16 ml). The reaction mixture was stirred for 2 hours at -10 C. and then poured into a cold mixture of 170 ml of 1N HCl and 170 ml of CH2 Cl2 with vigorous stirring. The layers were separated and the aqueous phase further extracted with CH2 Cl2 (2*200 ml). The combined organic layers were washed with water (3*100 ml) and then dried over MgSO4. Concentration produced 38.17 g of a crude oil. Purification by silica gel chromatography with 50:50 hexane:CH2 Cl2 as eluent gave 32.3 g of pure trichloromethyl carbinol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; water; dimethyl sulfoxide; | EXAMPLE 11 3-Chloro-5-methylbenzaldehyde To a cold solution (-60 C.) of oxalyl chloride (14.88 ml) in 300 ml of CH2 Cl2, dimethylsulfoxide (25.16 ml) in 75 ml of CH2 Cl2 was added followed by the addition of 3-chloro-5-methylbenzyl alcohol (23 g) in 100 ml of CH2 Cl2. To this cold mixture, triethylamine (103 ml) was slowly added (exothermic) over 20 minutes. The reaction mixture was then permitted to warm to room temperature over 1.5 hours. The mixture was then added to 1 L of water and the layers separated. The CH2 Cl2 layer was repeatedly washed with water and then dried with MgSO4. Concentration afforded 25.4 g of an oil which was chromatographed on silica gel. Elution with 60:40 hexane:CH2 Cl2 gave 20.01 g of pure 3-chloro-5-methylbenzaldehyde. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With 2-nitropropane; sodium hydride; In ethanol; for 3.0h; | [00327] To a solution of sodium metal ( 52 mg, 2.3mmol) in ethanol was added 2- nitropropane (0.23g, 2.4 mmole) followed by the addition of 3-chloro-5-methybenzylbromide (0.5g, 2.3 mmol). The reaction was allowed to stir for 3 hours and the precipitate formed was filtered off. The filtrate was concentrated under reduced pressure, redissolved in diethylether and washed with IN sodium hydroxide (twice), water, and dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified via silica gel chromatography using 10% dichloromethane and 90% petroleum ether, to give 0.15g of 3-chloro-5-methylbenzaldehyde (42%). 1H-NMR (CDCl3): 2.46 (s, 3H) 7.43(s, IH) 7.56 (s, IH) 7.68(s, IH), 9.92 (s, IH). |
With 2-nitropropane; sodium ethanolate; In ethanol; for 3.0h; | [0363] To a solution of sodium metal ( 52 mg, 2.3mmol) in ethanol was added 2- nitropropane (0.23g, 2.4 mmole) followed by the addition of 3-chloro-5-methybenzylbromide (0.5g, 2.3 mmol). The reaction was allowed to stir for 3 hours and the precipitate formed was filtered off. The filtrate was concentrated under reduced pressure, redissolved in diethylether and washed with IN sodium hydroxide (twice), water, and dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified via silica gel chromatography using 10% dichloromethane and 90% petroleum ether, to give 0.15g of 3-chloro-5-methylbenzaldehyde. 1H-NMR (CDCl3): 2.46 (s, 3H) 7.43(s, IH) 7.56 (s, lH) 7.68(s, IH), 9.92 (s, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | Preparation of 3-chloro-5-methylbenzaldehyde To a solution of sodium metal (52 mg, 2.3 mmol) in ethanol was added 2-nitropropane (0.23 g, 2.4 mmole) followed by the addition of 3-chloro-5-methybenzylbromide (0.5 g, 2.3 mmol). The reaction was allowed to stir for 3 hrs and the precipitate formed was filtered off. The filtrate was concentrated under reduced pressure, redissolved in diethylether and washed with 1N sodium hydroxide (twice), water, and dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified via silica gel chromatography using 10% dichloromethane and 90% petroleum ether, to give 0.15 g of 3-chloro-5-methylbenzaldehyde (42%). 1H-NMR (CDCl3): 2.46 (s, 3H) 7.43 (s, 1H) 7.56 (s, 1H) 7.68 (s, 1H), 9.92 (s, 1H). |