Structure of 3,5-Dichlorobenzoic acid
CAS No.: 51-36-5
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CAS No. : | 51-36-5 |
Formula : | C7H4Cl2O2 |
M.W : | 191.01 |
SMILES Code : | C1=C(C=C(C=C1C(O)=O)Cl)Cl |
MDL No. : | MFCD00002494 |
InChI Key : | CXKCZFDUOYMOOP-UHFFFAOYSA-N |
Pubchem ID : | 5811 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.42 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.61 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.0 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.69 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.52 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.25 |
Solubility | 0.107 mg/ml ; 0.00056 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.45 |
Solubility | 0.0681 mg/ml ; 0.000357 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
Solubility | 0.188 mg/ml ; 0.000986 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 |
-5.34 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 |
0.56 |
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) |
1.2 |
* 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 |
---|---|---|
86.9% | With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 2h; | 3,5-Dichlorobenzoic acid 2a (5.0 g, 26.32 mmol) was dissolved in 50 mL of tetrahydrofuran, and a borane tetrahydrofuran solution (52.6 mL, 52.64 mmol, 1 M/THF) was added dropwise at 0 C, and the mixture was reacted at room temperature for 2 hours. At 0 C, 50 mL of 10% sodium hydroxide solution was added to quench the reaction. The organic layer was washed with a saturated sodium chloride solution (50 mL). Methanol 6a (4.0 g, white solid), yield: 86.9% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
fe/Y-butyl 4-((3 ,5-dichlorobenzamido)methyl)-4-fluoropiperidine- 1 -carboxylate (4-5); 1-Hydroxybenzotriazole (6.27 g, 46.4 mmol) and 3,5-dichlorobenzoic acid (8.13 g, 42.6 mmol) were suspended in 210 mL dry CH2Cl2. Diisopropylethylamine (13.5 mL, 77.4 mmol) was added and all compounds went into solution. Amine 4-4 (10.4 g crude, 38.7 mmol) was added in 210 mL dry CH2CI2. PS-carbodiimide resin (59.5 g, 77.4 mmol) was then added and the mixture was stirred for 14 h. MP-carbonate resin (41.8 g, 120 mmol) was added and stirring was resumed for 3 h. The reaction was then filtered to remove resin and concentrated in vacuo, yielding 22.2 g of crude 4-5 as a viscous yellow oil. The crude amide 4-5 was carried forward. 1HNMR (CDCl3, 300 MHz): 7.94 (d, J= 1.8 Hz, IH),7.66 (d, J= 1.8 Hz, 2H), 6.44 (br t, IH)5 3.93 (br, 2H), 3.65 (br, 2H), 3.12 (br t, 2H), 1.83 (br t, 2H), 1.67 (m, 2H), 1.46 (s, 9H); MS (Electrospray): m/z 427.1 (M+Na), 349.1 (M-t-Bu+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.8% | The method for synthesizing 3,5-dichlorobenzyl chloride includes the following steps:1) Under a argon atmosphere, add 1 mol of 3,5-dichlorobenzoic acid, anhydrous THF and sodium borohydride to the reaction vessel.The temperature was raised to 60 C for 12 min, potassium chloride, polyethylene glycol 200 and sodium hydroxide aqueous solution of pH=14 were added to start ultrasonic assist, and the ultrasonic power and frequency were 420 W and 60 KHz, respectively.The control temperature is 110 C, the reaction pressure is maintained at 2 atmospheres, and the reaction is completed for 4 hours;The ratio of 3,5-dichlorobenzoic acid to sodium borohydride and potassium chloride is 1:0.42:1.4; 3,5-dichlorobenzoic acid and anhydrous THF,The amount ratio of the aqueous sodium hydroxide solution was 1 mmol: 2 ml: 0.8 ml.2) After cooling the system, about 2 times the volume of the reaction solution of ethyl acetate is added, the insoluble matter is removed by filtration, and the layers are separated. The organic phase is dried over anhydrous magnesium sulfate and concentrated.Recrystallization gave the product in a molar yield of 98.8% and HPLC purity 98.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10.5 g (74%) | With sodium tetrahydroborate; triethanolamine; | (i) 3,5-Dichlorobenzyl Alcohol Prepared according to the method described in Example X(i) above from 3,5-dichlorobenzoic acid (15.3 g; 80 mmol), TEA (8.9 g; 88 mmol), i-Bu chloroformate (12 g; 88 mmol) and NaBH4 (9.0 g; 240 mmol), yielding 10.5 g (74%) of sub-title compound. 1H-NMR (400 MHz; CDCl3): delta 7.27 (t, 1H); 7.28 (d, 2H); 4.68 (s, 2H). |