Structure of 99585-14-5
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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. : | 99585-14-5 |
Formula : | C9H9ClO2 |
M.W : | 184.62 |
SMILES Code : | O=C(OC)C1=C(C)C=CC=C1Cl |
MDL No. : | MFCD06204147 |
InChI Key : | RYUYMMGUQYRLQX-UHFFFAOYSA-N |
Pubchem ID : | 22935202 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.7 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.34 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.64 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.44 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.82 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.61 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.89 |
Solubility | 0.24 mg/ml ; 0.0013 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.84 |
Solubility | 0.265 mg/ml ; 0.00144 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.48 |
Solubility | 0.0616 mg/ml ; 0.000333 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 |
-5.55 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) |
1.54 |
* 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 |
---|---|---|
87% | Stage #1: at 0℃; for 0.75 h; Stage #2: at 20℃; |
A. A suspension of 2-chloro-6-methyl-benzoic acid (7.82 g, 45.8 MMOL) in thionyl chloride (20.0 mL, 275 MMOL), was immersed in an oil bath held at 85°C, and refluxed for 16 hours. The resulting pale brown solution was concentrated under reduced pressure to afford the acid chloride as a pale brown oil. This material was carried on to the ester formation without purification. The acid chloride (45.8 mmol from previous step) was dissolved in DICHLOROMETHANE (20 mL) and the mixture cooled in an ice bath. Methanol (10 mL, 247 MMOL) was added and the ice bath was then removed. HPLC of the reaction mixture 45 minutes after removal of the ice bath showed a 4: 1 mixture of starting acid: product ester. The reaction mixture was then treated with triethylamine (15 mL, 108 MMOL) dropwise over several minutes. The triethylamine addition was exothermic and led to the production of a lot of smoke in the reaction flask. After stirring overnight at ambient temperature HPLC indicated complete conversion to product. The reaction mixture was poured into a mixture of ether (200 mL) and saturated aqueous sodium hydrogen carbonate solution (100 mL). The layers were separated and the basic aqueous layer was extracted with ether (3 x 50 mL). The organic layers were combined and washed with brine, then dried (NA2SO4), filtered, and concentrated under reduced pressure to afford a yellow oil. The material was purified by flash chromatography eluting with a gradient from 0percent to 10percent ethyl acetate/hexane to afford 2-chloro-6-methylbenzoic acid methyl ester (7.38 g, 87percent yield) as a clear colorless liquid :'H-NMR (400 MHz, CDCI3) : 8 7.24-7. 19 (2H, m), 7.14-7. 08 (1H, m), 3.95 (3H, s), 2.32 (3H, s) ppm. |
72% | at 20℃; for 3 h; | Preparation XVII: 2-chloro-6-dimethylaminomethyl-benzoic acid. Step 1. Synthesis of 2-bromomethyl-6-chloro-benzoic acid methyl ester.2-Chloro-6-methyl benzoic acid (5.8 g, 34.0 mmoles) was suspended in dichloromethane (100 ml). To the suspension was added DMF (250 mg, 3.4 mmoles) and then dropwise oxalyl chloride (3.9 ml, 44.2 mmoles). The resultant solution was stirred at ambient temperature for 24 hours. Further DMF (250 mg, 3.4 EPO <DP n="151"/>mmoles) and oxalyl chloride (3.9ml, 44.2 mmoles) was added to the reaction mixture, and the resultant solution stirred for a further 24 hours at ambient temperature. The reaction mixture was concentrated in vacuo. The residue was dissolved in methanol (100 ml) and stirred at ambient temperature for 3 hours. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and sodium hydroxide solution (2N). The organic portion was washed with sodium hydroxide solution (2N), and then brine, dried (MgSO4), filtered and the concentrated in vacuo. The residue was purified by flash chromatography (eluent 3:5 EtOAc iPetrol to give 2-chloro-6-methyl-benzoic acid methyl ester as a yellow oil (4.5g, 72percent). |
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