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CAS No. : | 6322-83-4 |
Formula : | C15H12O4 |
M.W : | 256.25 |
SMILES Code : | O=C(O)COC1=CC=C(C(C2=CC=CC=C2)=O)C=C1 |
MDL No. : | MFCD02725448 |
InChI Key : | FQPOVZIKEBLFNG-UHFFFAOYSA-N |
Pubchem ID : | 80609 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.07 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 69.39 |
TPSA ? Topological Polar Surface Area: Calculated from | 63.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.89 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.38 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.86 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 2.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 2.3 |
Log S (ESOL):? ESOL: Topological method implemented from | -3.25 |
Solubility | 0.143 mg/ml ; 0.000556 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -3.67 |
Solubility | 0.0551 mg/ml ; 0.000215 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -4.39 |
Solubility | 0.0105 mg/ml ; 0.0000411 mol/l |
Class? Solubility class: Log S scale | Moderately 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 | -5.96 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 | 0.0 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 1.85 |
* 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 |
---|---|---|
74% | Stage #1: With sodium hydroxide In ethanol at 20℃; Stage #2: With hydrogenchloride In water at 0℃; | General procedure: A solution of NaOH 1N (3.9 mmol) was added to esters 7-16(3.0 mmol) in EtOH (20 mL), and the mixture was stirred at r.t. for 10-15 h. The solvent was removed under reducedpressure and the residue was poured into water (20 mL) andacidified with conc HCl at 0 °C. The aqueous layer was extractedwith dichloromethane (3 20 mL) and then the organiclayer was dried over Na2SO4 and concentrated underreduced pressure. The residue was purified by crystallizationwith cyclohexane or chloroform affording desired acids 17-26 with good yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With water; lithium hydroxide In tetrahydrofuran; methanolHeating | General procedure: To a solution of 5a-i (1.0 eq.) in a mixture of equal amounts of THF and methanol (0.5 M solution) was added an aqueous 1 M solution of LiOH (5.0 eq.). After 1 hour at 100 °C th esaponification of the esters 6a-q was completed shown by TLC (EtOAc/Pet. ether 1/3). While the mixture was cooled on ice, the pH was adjusted to pH = 1 using a 2 M HCl solution (aq.). The resulting precipitate was collected by filtration, washed with water, Pet. ether and co-evaporated with acetone to dryness. 1.7.1. 2-(4-Benzoylphenoxy)acetic acid (6a).[21] White solids 1.37 g, yield = 95percent. 1H NMR (400 MHz, CDCl3 + drop of DMSO): δ 9.50 (s br, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 7.6 Hz, 2H), 7.58 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 4.69 (s, 2H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | General procedure: A solution of NaOH 1N (3.9 mmol) was added to esters 7-16(3.0 mmol) in EtOH (20 mL), and the mixture was stirred at r.t. for 10-15 h. The solvent was removed under reducedpressure and the residue was poured into water (20 mL) andacidified with conc HCl at 0 C. The aqueous layer was extractedwith dichloromethane (3 20 mL) and then the organiclayer was dried over Na2SO4 and concentrated underreduced pressure. The residue was purified by crystallizationwith cyclohexane or chloroform affording desired acids 17-26 with good yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With toluene-4-sulfonic acid; In N,N-dimethyl acetamide; toluene;Reflux; | COMPINI-2 is a comparative initiator represented by the following formula: [Show Image] COMPINI-2 was synthesized as follows: [Show Image] (4-benzoylphenoxy)-acetic acid was prepared according to Chen et al., Macromolecular Chemistry and Physics (2007), 208(15), 1694-1706. 25.6 g (0.10 mol) (4-benzoylphenoxy)-acetic acid was dissolved in 100 mL toluene and 30 mL dimethyl acetamide. 14.8 g (0.20 mol) sec. butanol and 28 g (0.15 mol) p.-toluene sulfonic acid were added. The reaction mixture was refluxed under azeotropical removal of water. 250 mL ethyl acetate was added and the mixture was extracted with 200 mL 1 N NaOH. The organic fraction was dried over MgSO4 and the solvent was removed under reduced pressure. COMPINI-2 was isolated as a white crystalline compound. 29.8 g (95%) of COMPINI-2 was isolated. |
95% | With toluene-4-sulfonic acid; In N,N-dimethyl acetamide; toluene;Reflux; | COMPINI-2 was synthesized as follows: [Show Image] (4-benzoylphenoxy)-acetic acid was prepared according to Chen et al., Macromolecular Chemistry and Physics (2007), 208(15), 1694-1706. 25.6 g (0.10 mol) (4-benzoylphenoxy)-acetic acid was dissolved in 100 mL toluene and 30 mL dimethyl acetamide. 14.8 g (0.20 mol) sec. butanol and 28 g (0.15 mol) p.-toluene sulfonic acid were added. The reaction mixture was refluxed under azeotropical removal of water. 250 mL ethyl acetate was added and the mixture was extracted with 200 mL 1 N NaOH. The organic fraction was dried over MgSO4 and the solvent was removed under reduced pressure. COMPINI-2 was isolated as a white crystalline compound. 29.8 g (95%) of COMPINI-2 was isolated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; | General Procedure: 3 equivalents of an acid and HOBt (21.7 mg, .157 mmol, 3 equiv.) were added to asolution of B (20 mg, 0.0523 mmol, 1 equiv) in DMF (1.0 mL). EDCI (26.5 mg, .157mmol, 3 equiv.) was then added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was then partitioned between EtOAc and saturated sodium carbonate, washed with ammonium chloride, brine, and dried over Na2SO4. The organic phase was concentrated and subjected to a 1:1 solution of TFA/CH2Cl2 for 1 hour at room temperature. After 1 hour, the reaction was concentrated and purified by reverse phaseHPLC to afford the final compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation Example 73 Synthesis of Compound 73 (0336) (0337) Hydroxybenzophenone 2, methyl chloroacetate and K2CO3 were mixed in acetone, refluxed and stirred to afford ester 3 (step a). After completion of the reaction, an aqueous NaOH solution was added thereto, followed by acidification with HCl to obtain carboxylic acid 4 (step b). Then, 4-amino-1-benzylpiperidine was added to the carboxylic acid 4, followed by conducting the reaction in the same manner as in the preparation example 12, using carbonyl diimidazole (CDI) as a condensing agent, to obtain Compound 73. (0338) 1H-NMR (600 MHz, DMSO-d6): delta 8.04 p.p.m. (d, j=8.0 Hz, 1H), 7.74 (d, J=9.1 Hz, 2H), 7.68 (d, J=7.1 Hz, 2H), 7.65 (t, j=7.6 Hz, 1H), 7.55 (t, j=5.8 Hz, 2H), 7.27-7.32 (m, 4H), 7.23 (t, J=7.1 Hz, 1H), 7.09 (d, J=9.0 Hz, 2H), 4.58 (s, 2H), 3.63 (m, 1H), 3.44 (s, 2H), 2.74 (d, J=11.7 Hz, 2H), 1.99 (t, J=11.5 Hz, 2H), 1.70 (d, J=9.8 Hz, 2H), 1.50 p.p.m. (dq, J1=3.0 Hz, J2=11.9 Hz, 2H); (0339) 13C-NMR (150 MHz, DMSO-d6): delta 194.4, 166.2, 161.5, 138.6, 137.7, 132.2, 132.0, 129.8, 129.3, 128.7, 128.5, 128.1, 126.8, 114.6, 66.9, 62.1, 51.9, 46.1, 31.4 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With water; lithium hydroxide; In tetrahydrofuran; methanol;Heating; | General procedure: To a solution of 5a-i (1.0 eq.) in a mixture of equal amounts of THF and methanol (0.5 M solution) was added an aqueous 1 M solution of LiOH (5.0 eq.). After 1 hour at 100 C th esaponification of the esters 6a-q was completed shown by TLC (EtOAc/Pet. ether 1/3). While the mixture was cooled on ice, the pH was adjusted to pH = 1 using a 2 M HCl solution (aq.). The resulting precipitate was collected by filtration, washed with water, Pet. ether and co-evaporated with acetone to dryness. 1.7.1. 2-(4-Benzoylphenoxy)acetic acid (6a).[21] White solids 1.37 g, yield = 95%. 1H NMR (400 MHz, CDCl3 + drop of DMSO): delta 9.50 (s br, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 7.6 Hz, 2H), 7.58 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 4.69 (s, 2H) ppm. |
With sodium hydroxide; In water; | Preparation Example 73 Synthesis of Compound 73 (0336) (0337) Hydroxybenzophenone 2, methyl chloroacetate and K2CO3 were mixed in acetone, refluxed and stirred to afford ester 3 (step a). After completion of the reaction, an aqueous NaOH solution was added thereto, followed by acidification with HCl to obtain carboxylic acid 4 (step b). Then, 4-amino-1-benzylpiperidine was added to the carboxylic acid 4, followed by conducting the reaction in the same manner as in the preparation example 12, using carbonyl diimidazole (CDI) as a condensing agent, to obtain Compound 73. (0338) 1H-NMR (600 MHz, DMSO-d6): delta 8.04 p.p.m. (d, j=8.0 Hz, 1H), 7.74 (d, J=9.1 Hz, 2H), 7.68 (d, J=7.1 Hz, 2H), 7.65 (t, j=7.6 Hz, 1H), 7.55 (t, j=5.8 Hz, 2H), 7.27-7.32 (m, 4H), 7.23 (t, J=7.1 Hz, 1H), 7.09 (d, J=9.0 Hz, 2H), 4.58 (s, 2H), 3.63 (m, 1H), 3.44 (s, 2H), 2.74 (d, J=11.7 Hz, 2H), 1.99 (t, J=11.5 Hz, 2H), 1.70 (d, J=9.8 Hz, 2H), 1.50 p.p.m. (dq, J1=3.0 Hz, J2=11.9 Hz, 2H); (0339) 13C-NMR (150 MHz, DMSO-d6): delta 194.4, 166.2, 161.5, 138.6, 137.7, 132.2, 132.0, 129.8, 129.3, 128.7, 128.5, 128.1, 126.8, 114.6, 66.9, 62.1, 51.9, 46.1, 31.4 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; | General procedure: To a solution of 6a-r (1.0 equiv.) and Et3N (1.5 equiv.) in DMF (0.125 M) was added 3-aminopyridine (1.1 equiv.) and HATU (1.1 equiv.) or EDCIHCl (7e and 7l). The mixturewas stirred at room temperature for 20 h. The mixture was separated between ethyl acetate and water. The organic layer was washed with water twice, brine, dried over MgSO4 and concentrated. Column chromatography using mixtures of 5% methanol/dichloromethane or EtOAc:-Pet.ether 2:1 gave the pure desired products. 4.2.1 2-(4-Benzoylphenoxy)-N-(pyridin-3-yl)acetamide (7a) [19] White solid, 211 mg, yield = 69%. 1H NMR (400 MHz, CDCl3): delta 8.70 (s br, 1H), 8.44 (s br, 1H), 8.40 (s br, 1H), 8.22 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 7.6 Hz, 2H), 7.60 (t, J = 7.6 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.34 (d, J = 7.2 Hz, 1H), 7.09 (d, J = 8.8 Hz, 2H), 4.74 (s, 2H) ppm; 13C NMR (101 MHz, CDCl3): delta 195.3, 166.4, 160.2, 137.4, 132.4, 132.2, 131.2, 129.5, 128.1, 127.8, 114.1, 67.2 ppm; HPLC tR = 7.28 min purity 100%; ESI-MS: 333.13 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | Preparation Example 12 Synthesis of Compound 12 (0213) (0214) A vial was charged with a carboxylic acid (326 mg, 1 equiv.) and dry DMF (1 mL). To the stirred reaction mixture, N,N-carbodiimidazole (237 mg, 1.2 equiv.) was added. After 1 h of stirring the vial was open and the reaction mixture was left for 2 h in a drying oven at 60 C. Then an amine (286 mg, 1 equiv.) was added, the vial was firmly closed, and the reaction mixture was stirred. The reaction vial was placed into a water bath and left at 100 C. for 1 h. The reaction mixture was cooled to room temperature and water was added until the vial was full. Then the vial was sonicated. In case a crystalline precipitate was formed, the vial was subjected to the filtration. In case an oily product was formed, the vial was left overnight, then the water layer was removed and 2-propanol (1 mL) was added to cause the crystallization. The precipitate was filtered, washed twice with a sodium carbonate solution, and then washed with a water/2-propanol (1:1) solution. The crude product was purified by chromatography (silica gel, chloroform:2-propanol=4:1). The yield was 63 mg (11%). |
Tags: 6322-83-4 synthesis path| 6322-83-4 SDS| 6322-83-4 COA| 6322-83-4 purity| 6322-83-4 application| 6322-83-4 NMR| 6322-83-4 COA| 6322-83-4 structure
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H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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