Structure of 644-36-0
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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. : | 644-36-0 |
Formula : | C9H10O2 |
M.W : | 150.17 |
SMILES Code : | C1=CC=CC(=C1CC(O)=O)C |
MDL No. : | MFCD00004328 |
InChI Key : | RZWGTXHSYZGXKF-UHFFFAOYSA-N |
Pubchem ID : | 69519 |
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 | 0.22 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.95 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.43 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.93 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.62 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.98 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.01 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.79 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.26 |
Solubility | 0.828 mg/ml ; 0.00551 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.34 |
Solubility | 0.691 mg/ml ; 0.0046 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.54 |
Solubility | 0.429 mg/ml ; 0.00286 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 |
-5.85 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) |
1.23 |
* 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 |
---|---|---|
42% | With sulfuric acid; nitric acid; In dichloromethane; at -20 - 20℃; | Intermediate 80A: Preparation of 2-(2-methyl-5-nitrophenyl)acetic acid [00224] A solution of 2-o-tolylacetic acid (3.54 g, 23.6 mmol) in DCM (12 mL) was added to a pre-cooled mixture of concentrated sulfuric acid (10 mL, 188 mmol) and 90% nitric acid (1 mL, 22.4 mmol) at - 20 0C. The reaction mixture was stirred at - 20 0C for 30 minutes, then slowly warmed to room temperature and stirred overnight. The reaction mixture was poured into ice-water. The white solid was collected by filtration, rinsed with water, and concentrated. The solid was triturated with ether and filtered to obtain Intermediate 8OA (2.4 g, 42%) as a white solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 12.62 (1 H, br. s.), 8.13 (1 H, d, J = 2.51 Hz), 8.04 (1 H, dd, J = 8.28, 2.51 Hz), 7.47 (1 H, d, J = 8.53 Hz), 3.80 (2 H, s), 2.34 (3 H, s). |
34.6% | The starting material 2-methyl-phenylacetic acid (200.0 g, 1.33 mol)Was dissolved in dichloromethane (700 mL)0 C below slowly addedConcentrated sulfuric acid (584 mL),After the addition reaction was continued for 0.5 hours,Then concentrated nitric acid (30 mL)Maintain the temperature at -2 ~ 3 reaction 16 hours;After the reaction,Poured into 500 mL of water,Extracted with dichloromethane, dried,Concentrated to give Compound 1-2 (90.0 g) in a yield of 34.6%. | |
32% | With sulfuric acid; nitric acid; In dichloromethane; at -10℃; for 1h; | Step 1: a 500 mL round bottom flask was charged with conc. sulfuric acid (130 mL) and cooled to -10C. A solution of o-tolyacetic acid (10 g, 66.58 mmol) in CH2CI2 (35 mL) was added dropwise. After that, a solution of conc. sulfuric acid(27 mL) and nitric acid (2.7 mL) was slowly added dropwise. The reaction mixture was stirred at -10C for 1 h and then poured onto ice. The aqueous phase was extracted with EtOAc. The organic layer was washed with water and brine, dried, filtered and the solution was concentrated under reduced pressure. The resulting solid was triturated in Et20 and filtered off to afford 2-(2-methyl-5-nitrophenyl)acetic acid as white solid (4.21 g, 32%). |
With sulfuric acid; nitric acid; In dichloromethane; | A. Acylating Reagent (2-Methyl-5-nitrophenyl)acetic acid A 1 L round bottom flask was charged with conc. sulfuric acid (500 mL) and cooled to -12 C. (ethyleneglycol-dry ice). (2-Methylphenyl)acetic acid (35.4 g, 0.24 mol) dissolved in dichloromethane (120 mL) was added during 10 minutes and the mixture was then treated dropwise during two hours with a pre-cooled (ethylene glycol-dry ice) solution of conc. sulfuric acid (100 mL) and 100% nitric acid (10 mL). The reaction mixture was stirred for one hour at -12 C. and then poured on ice. The aqueous phase was extracted with ethyl acetate (3*1 L). The combined organic phases were washed with brine (2*1L) and water (2*1 L), dried (Na2SO4) and concentrated in vacuo to give the 38.1 g crude mixture (38 g). 1H NMR showed a 70:30 mixture of the title compound and (2-methyl-3-nitrophenyl)acetic acid, and the title compound was purified by trituration with diethyl ether. | |
With sulfuric acid; nitric acid; In dichloromethane; at -20 - 20℃; for 0.75h; | - Step 1: a solution of o-tolyacetic acid (5.0 g, 33.29 mmol), in CH2CI2 (15 mL) was added dropwise to a pre-cooled mixture of conc. sulfuric acid (26 mL, 266.3 mmol) and 99.5% nitric acid (1.35 mL, 31.63 mmol) at -20C. The reaction mixture was stirred at that temperature for 30 mm, then slowly warmed to rt and stirred for 1 5h. The reaction mixture was poured into ice-water. The white solid was collected by filtration and washed with water. The solid was triturated with Et20 and filtered to obtain the mono and di-nitration products in a 1:1 ratio (4.78 g), that will be separated after the next esterification step. |
A221806 [19806-17-8]
2,2'-(1,3-Phenylene)diacetic acid
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