Structure of Methyl (2-nitrophenyl)acetate
CAS No.: 30095-98-8
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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. : | 30095-98-8 |
Formula : | C9H9NO4 |
M.W : | 195.17 |
SMILES Code : | O=C(OC)CC1=CC=CC=C1[N+]([O-])=O |
MDL No. : | MFCD00968465 |
InChI Key : | SWMFAAPTSMVULA-UHFFFAOYSA-N |
Pubchem ID : | 520464 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 51.13 |
TPSA ? Topological Polar Surface Area: Calculated from |
72.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.79 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.91 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.31 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.89 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.16 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.31 |
Solubility | 0.964 mg/ml ; 0.00494 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.05 |
Solubility | 0.175 mg/ml ; 0.000896 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.26 |
Solubility | 1.07 mg/ml ; 0.00546 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 |
No |
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 |
-6.13 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 |
2.0 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) |
1.95 |
* 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 |
---|---|---|
98% | With palladium on activated charcoal; hydrogen; In toluene; at 5℃; under 760.051 Torr; | Compound 2 (97.6 g, 0.5 mol),Pd/C (0.98g) and toluene (200mL) were placed in the reaction flask.Hydrogen was passed through a hydrogenation reaction at normal pressure of 5 C overnight.After the reaction,filter,Wash with a small amount of toluene,Combine the filtrate and the wash solution,Recovering toluene,Precipitating solids,Vacuum drying,The pale yellow liquid was Intermediate 3 (80.9 g, 98%). |
97% | With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; | Preparation of methyl 2-(2-aminophenyl)acetate (Compound 6-1) [00231j A mixture of Compound 1-2 (9.75 g, 50 mmol), 10% palladiumlactivecarbon catalyst (dry, 530 mg, 5 mmol) in methanol (100 mL) was stirred under hydrogen atmosphere at room temperature for overnight. The reaction mixture was filtered to remove palladiumlactive carbon catalyst and the filtrate was concentrated to give Compound 6-1 (8.02 g, yield: 97%) as a pale yellow oil. MS (ES): mlz:166[M+H]. ?H NMR (400 MHz, DMSO-d6) oe: 6.94 (m, 2H), 6.64 (d, 1H, J 8.0 Hz),6.51 (m, 1H), 4.88 (s, 2H), 3.59 (s, 3H), 3.52 (s, 2H). |
97% | With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; under 760.051 Torr; | Preparation of methyl 2-(2-aminophenyl)acetate (Compound 11-3)[00269j A mixture of methyl 2-(2-nitrophenyl)acetate (Compound 11-2, 9.75 g, 50 mmol), 10% palladiumlactive carbon catalyst (dry, 530 mg, 5 mmol) in methanol (100 mL) was stirred under H2 (1 atm.) at room temperature overnight. The reaction mixture was filtered to remove palladiumlactive carbon catalyst and the filtrate was concentrated to give the desired product methyl 2-(2-aminophenyl)acetate (Compound 11-3, 8.02 g, yield: 97%) as a pale yellow oil. MS (ESI): mlz: 166[M+H]. ?H NMR (400 MHz, DMSO-d6) oe: 6.94 (m, 2H), 6.64 (d, 1H, J= 8.0 Hz), 6.51 (m, 1H), 4.88 (s, 2H), 3.59 (s, 3H), 3.52 (s, 2H). |
67% | With hydrogen;palladium 10% on activated carbon; In ethyl acetate; at 20℃; for 2h; | The 2-nitrophenyl acid methyl ester (1 g, 5.13 mmol) was dissolved in 20 mL of EA and 0.3 g of Pd/C 10% was suspended into the solution, the reaction mixture was under hydrogen atmosphere at room temperature. After 2h the reaction was completed by TLC analysis (DCM: EA 60; 40) the Pd/C 10% was removed by filtration and the solvent by reduced pressure; to yield a colorless oil 0.67 g (67%). |
8.5 g (100%) | palladium-carbon; In methanol; | B. Methyl 2-aminophenylacetate. Methyl 2-nitrophenylacetate (10.1 g, 51.2 mmol) in 125 mL of methanol containing 221 mg of 10% Pd/C was placed on the Parr hydrogenator at 40 psi. After 5 h the mixture was filtered through celite and evaporated under reduced pressure to give a clear red oil. The solvent was evaporated under reduced pressure to give 8.5 g (100%) of methyl 2-aminophenylacetate as a clear red oil. TLC (silica, EtOAc/hexanes): Rf=0.24. 1H NMR (400MHz, CDCl3): 7.21 (m, 2H), 6.86 (m, 2H), 3.81 (s, 3H), 3.70 (s, 2H). |
With hydrogen;platinum(IV) oxide; In methanol; under 2585.81 - 2844.39 Torr; for 25.5h; | B. (2-Amino-phenyl) acetic acid methyl ester; The title A compound, (2-nitro-phenyl)-acetic acid methyl ester (5.0 g, 25.6 mmol) is dissolved in MeOH (125 mL) in a Parr Bottle. It is purged with nitrogen, then added Pt02 (185 mg), then placed on a Parr Shaker under 50 to 55 psi of hydrogen with shaking for 25.5 h. The reaction is opened and filtered through celite, and concentrated to yield (2-amino- phenyl) acetic acid methyl ester as an amber oil : [M+1] + = 166. | |
With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃;Inert atmosphere; | Add Pd/C (10%, 800 mg) to a solution of methyl 2-(2-nitrophenyl)acetate (7.5 g, 38.5 mmol) in methanol (50 mL) under N2, then flush with H2, stir the reaction under atmosphere at room temperature overnight. Remove the hydrogen; filter off the solid, concentrate the filtrate under reduced pressure to obtain the crude product (4.8 g, 76.2%) which is used directly without further purification. MS: (M+l):166 | |
With palladium 10% on activated carbon; hydrogen; In methanol; at 25℃;Inert atmosphere; | Add Pd/C (10%, 800 mg) to a solution of methyl 2-(2-nitrophenyl)acetate (7.5 g, 38.5 mmol) in methanol (50 mL) under N2, then flush with H2, stir the reaction under H2 atmosphere at room temperature overnight. Remove the hydrogen; filter off the solid, concentrate the filtrate under reduced pressure to obtain the crude product (4.8 g, 76.2%) which is used directly without further purification. MS: (M+1):166. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With magnesium sulfate; triethylamine;palladium; In toluene; | To a solution of methyl 2-nitrophenylacetate, (6.04 kg) in toluene (100 l) is added anhydrous magnesium sulfate (2.00 kg) and then 5% palladium-on-charcoal (125 g). The mixture is then stirred and hydrogenated, keeping the temperature below 40 by regulation of the stirring rate and input of hydrogen gas. After the addition is complete, the mixture is filtered. The filtrate containing <strong>[35613-44-6]methyl 2-aminophenylacetate</strong> is cooled to -20 and triethylamine (3.75 kg) is added all at once with stirring. This is followed by the slow addition of a solution of methanesulfonyl chloride (3.91 kg) in toluene (4.5L), keeping the temperature between -2 and 5. After stirring at -2 for 1 hour, the mixture is filtered and washed with toluene (10 l). The filter cake is then slurried with water (90 l) for 90 minutes, filtered, and washed with water (45 l) and methanol (8 l). The solid is dried at 50 in vacuo overnight to yield methyl 2-(methylsulfonylamino)phenylacetate, mp 73-75. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydroborate; In tetrahydrofuran; methanol; for 6h;Reflux; | General procedure: To a mixture of LiAlH4 (15 mmol) in anhydrous THF (25 mL) in an ice-bath was added dropwise a solution of phenylacetic acids (15 mmol) in THF (8 mL). This mixture was stirred at room temperature for 30 min, and then heated to reflux for 4 h. After it was cooled to room temperature, water (0.5 mL) was added, and then NaOH (15percent, 0.5 mL) and water (1.5 mL) were added in sequence. After stirring for another 30 min, the mixture was filtered, dried over anhydrous Na2SO4 and concentrated to give crude products. Pure phenylethyl alcohols were obtained in 50-85percent yield by column chromatography. Alternative method: To a solution of phenylacetic acids (15 mmol) in MeOH (30 mL) was added SOCl2 (30 mmol). This mixture was heated to reflux for 3 h before evaporation. The residue was dissolved in DCM (30 mL), washed with aqueous NaHCO3, water and brine, dried over anhydrous Na2SO4, and concentrated to give 100percent yield of crude methyl phenylacetates which were used to next step without further purification. To a solution of the methyl phenylacetates in THF (30 mL) was added NaBH4 (60 mmol). When the mixture was heated to gently reflux, MeOH (1.0 mL) was added dropwise from a syringe over 5 min. After refluxing for another 6 h, the mixture was cooled to room temperature and poured into 30 mL ice water, and extracted with EtOAc (30 mL × 2). The combined organic phase was washed with brine, dried over anhydrous Na2SO4, and concentrated to give crude products. Pure phenylethyl alcohols were obtained in 70-85percent yield by column chromatography. |
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