Structure of 94-02-0
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CAS No. : | 94-02-0 |
Formula : | C11H12O3 |
M.W : | 192.21 |
SMILES Code : | O=C(OCC)CC(C1=CC=CC=C1)=O |
MDL No. : | MFCD00009196 |
InChI Key : | GKKZMYDNDDMXSE-UHFFFAOYSA-N |
Pubchem ID : | 7170 |
GHS Pictogram: |
![]() |
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 | 0.27 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 52.34 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.37 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.93 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.82 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.3 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.2 |
Solubility | 1.22 mg/ml ; 0.00635 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.4 |
Solubility | 0.761 mg/ml ; 0.00396 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.23 |
Solubility | 0.112 mg/ml ; 0.000582 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 |
-6.14 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 |
1.0 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) |
1.46 |
* 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% | Stage #1: for 1 h; Heating / reflux Stage #2: at 45℃; Heating / reflux |
Intermediate 1A : Preparation of 4-chloro-6-phenylpyrimidin-2-amine; A suspension of guanidine carbonate (3.60 g, 20 mmol) in ethanol (120 mL) and toluene (20 mL) was refluxed under nitrogen for 1 h, during which time about 50 mL of solvent was removed by distillation. After the mixture was cooled to 45 °C, ethyl 3-oxo-3- phenylpropanoate (7.68 g, 40 mmol) was added and the solution was heated at reflux overnight. The desired product precipitated as a white solid during the reaction. Water (50 mL) was added to the reaction and the mixture was refluxed for an additional 30 min. After cooling to rt, the mixture was neutralized with 1N HC1 and placed in the refrigerator for 6 h. The solid was filtered, washed with water followed by ether and dried at 60 °C under vacuum to give the product as white solid (6.45 g, 86percent). MS ES: 188 (M+H) +, calcd 188; RT = 0.91 min; TLC (CH2C12/2M NH3 in MeOH 95/5) Rf = 0.10. A mixture of the above product (6.0 g, 32 mmol) and POC13 (100 mL) was heated at reflux for 1 h. The majority of the POC13 was removed in vacuo and the residue was diluted with EtOAc and poured over an ice/saturated NaHC03 solution. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried (Na2SO4), and concentrated. The crude organic concentrate was re-crystallized from EtOAc/ether to give the product 1A as an off-white powder (2. 8 g, 43percent). MS ES: 206 (M+H) +, calcd 206; RT = 2.49 min; TLC (CH2C12/2M NH3 in MeOH 95/5) Rf = 0.72. (Reference 1: H. L. Skulnick, S. D. Weed, E. E. Edison, H. E. Renis, W. Wierenga, and D. A. Stringfellow, J ; Med. Cllem. 1985, 28,1854-1869). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | at 80℃; Inert atmosphere | General procedure: To a suspension of guanidine carbonate (1.5-5 eq) in ethanol (2 mL/mmol) was added γ-aryl-β-ketoester (1.43-26.6 mmol), and the reaction mixture heated at 80 °C for 15-64 h. Followingreaction completion by TLC, the mixture was cooled to ambient temperature, filtered and thesolid triturated with water (5-20 mL) and acetone (5-20 mL) to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | 15.0 ml of pyridine are added to a solution of 173.0 g (0.9 mol) of ETHYLBENZOYL acetate in 3.2 litres of xylene, and the mixture is heated to 130-135°C. At that temperature, 107.0 g (0.75 mol) of 4-chloro-1, 3-phenylenediamine are added in portions to the solution and the ethynol that is liberated is distilled off continuously. After 5 hours, the reddish-brown solution is cooled to 25°C and 14.3 g (75 mol) of p-toluenesulfonic acid are added thereto. The resulting green suspension is then boiled for 6 hours under reflux, the water of reaction being distilled off. The suspension, which is now yellow, is allowed to cool to room tempera- ture. Filtration is then carried out, the precipitate is washed with a total of 500 mi of ethanol in three portions, and the crude product is dried for 20 hours at 80°C under a laboratory vacuum. There are obtained 179 G (0. 66 mol, yield 88 percent of theory) of A beige-brown powder of formula which, after recrystallisation from acetic acid, is in the form of white crystals having a melting point of 327°C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | To a solution of [1-AMINO-PYRROLIDINE-2-ONE] hydrochloride (3.8 g, 27.8 mmol) (WO 02/094833) add ethylbenzoylacetate (4.3 mL, 25 mmol) followed by pyridine (10 mL) at room temperature under nitrogen. Stir the mixture at room temperature for 20 hours and then, dilute with water (50 mL) and extract with toluene (2 x 50 mL). Dry the combined organic layers [(MGS04)] and concentrate in vacuo to give a brown oil, 6.23 g, [82%] yield, and treat with NaOEt (freshly prepared, 3.1 g, 45.4 mmol, 2 equiv) in toluene at [120C] for 8 hours. Cool the mixture to room temperature and add water (100 mL) and concentrated HCl until a pH of 4 is reached. Extract the mixture with EtOAc (3 x 200 mL) and dry [(MGS04)] the combined organic layers and concentrate in vacuo. Purify the residue in a biotage system (eluent: [CH2C12/MEOH] 40: 1) to obtain a yellow solid, 1. [8] g, 36% yield. MS [(ES+)] : [NEZ] = 257.1 [(M+H) +] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To 5 ml of methanol, 4 g of sodium methoxide (28percent methanol solution), 0.75 g of <strong>[57297-29-7]cyclopropanecarboxamidine hydrochloride</strong> and 1 g of benzoylacetic acid ethyl ester were added. This mixture was heated under reflux for 20 hours. The reaction mixture was left standing to cool and then concentrated. To the residue, 10percent hydrochloric acid was added, followed by extraction three times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and then concentrated. The residue was washed with hexane to obtain 0.39 g of 2- cyclopropyl-6-phenylpyrimidin-4-ol . 2-cyclopropyl-6-phenylpyrimidin-4-ol1H-NMR (DMSO-de): 1.04-1.16 (m, 4H) , 1.93-1.99 (m, IH) ,6.64(s, IH), 7.43-7.47 (m, 3H), 7.94-7.99 (m, 2H) , 12.67(bs,lH) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[0498] Ethyl 3-oxo-3-phenylpropanoate (150 mmol) and cesium carbonate (C52CO3, 226 mmol) were dissolved in DMSO (50 ml). The reaction mixture was stirred at rt for 10 minutes at which time potassium iodide were added (KI, 150 mmol) and 4-(bromomethyl)- benzenesulfonamides (165 mmol). The resulting mixture was stirred at rt for 1 h. Upon completion as detected by LCMS, the reaction mixture was diluted with a large excess of ethyl acetate and filtered through celite. The filtrate was washed with 1 M HC1, sat aq NH4C1 and brine, dried over Na2504, filtered, and concetrated under reduced pressure. The residue was purified directly on silica using gradient elution (20-40 percent ethyl acetate in hexanes over 16 CV). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | General procedure: In a 50 mL flask, a mixture of hydrazine hydrate 1 (1 mmol), beta-keto ester 2 (acetylacetic ether or ethyl benzoylacetate) (1 mmol) was stirred at room temperature (78C) for 5 minutes. And then, 2-hydroxynaphthalene-1,4-dione 3 (1 mmol), isatins 4 (1 mmol), MgCl2 (0.1 mmol) and 5 mL ethanol were added to it. The mixture was stirred at 78C for the appropriate time. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature, 5 mL water was added to it. Then the precipitated products were filtered and washed with cold ethanol (3 mL×2) to afford the pure products as solid powder in good to excellent yields without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium hydroxide; In acetonitrile; at 20℃; for 7h; | Cyclopropylamidine hydrochloride and sodium hydroxide into a 25mL round bottom flask, into the 3mL acetonitrile solvent, pre-service And in addition to acid, get free amidine. Then, ethyl benzoylacetate and perfluoroiodobutane were successively added at room temperature. room Within the light and room temperature reaction 7h, TLC monitoring reaction end, stop the reaction, the mixture. [0109] Ethyl benzoylacetate: Perfluoroiodobutane: cyclopropyl formamidine hydrochloride: sodium hydroxide = 1.0: 1.1: 1.1: 4.1; [0110] 2. The mixture was extracted three times with water, the organic phases were combined and the organic solvent was removed by distillation under reduced pressure to give crude product. [0111] 3. The crude product was chromatographed on silica gel eluting with eluent (petroleum ether: ethyl acetate = 30: 1 (nu: nu)), A white solid was obtained as the product ethyl-2-cyclopropyl-4-perfluoropropyl-6-phenylpyrimidine-5-carboxylate in 86percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | at 180℃; for 24h; | 3-dimethylaminophenol (500 mg, 3.64 mmol, 1 equiv.) and ethyl benzoylacetate (1.10 mL, 6.37 mmol, 1.75 equiv.) were combined in a 10 mL flask and heated at 180 °C for 24 h. The solution was cooled to room temperature, evaporated onto silica gel and purified via columnchromatography with a 50: 1 to 1 :4, followed by a 6: 1 to 1 : 1 hexanes:ethyl acetate gradient. The procedure gave a beige solid (493 mg, 1.86 mmol, 51percent). NMR (500 MHz, Chloroform-i/) delta 8.01 (d, J= 9.0 Hz, 1H), 7.93 - 7.84 (m, 2H), 7.51 - 7.44 (m, 3H), 6.73 (dd, J= 9.0, 2.4 Hz, 1H), 6.67 (s, 1H), 6.55 (d, J= 2.4 Hz, 1H), 3.07 (s, 6H).13C NMR (126 MHz, Chlorofornw/) delta 177.94, 162.26, 158.45, 154.23, 132.34, 131.11, 128.97, 126.60, 126.11, 113.70, 110.87, 107.31, 40.26. MS (ESI+): calculated for Ci7Hi6N02+[M+H]+: 266.3; found: 266.1. Absorbance(CH2CI2): 229 nm, 274nm, 358 nm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tert.-butylhydroperoxide; N-iodo-succinimide; sodium carbonate; In N,N-dimethyl acetamide; at 50℃; for 16h;Inert atmosphere; | General procedure: benzylamines (1, 0.2 mmol), 1,3-dicarbonyl derivatives (2,0.3 mmol), NIS (0.4 mmol), TBHP (0.6 mmol), Na2CO3 (0.4 mmol) were mixed under N2 atmosphere in 2 mL DMA. The reaction tube was heated in an oil bath at 50 C for 16 hours. After completion of the reaction, the reaction mixture was extracted with EtOAc (15 mL × 3), and the solvent was removed under reduced pressure. The remaining crude product was then purified through column chromatography using silica gel (ethyl acetate/petroleum ether = 1/10) to afford 3. |
Tags: 94-02-0 synthesis path| 94-02-0 SDS| 94-02-0 COA| 94-02-0 purity| 94-02-0 application| 94-02-0 NMR| 94-02-0 COA| 94-02-0 structure
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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 |
Sorry,this product has been discontinued.
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