Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 609-08-5 | MDL No. : | MFCD00009162 |
Formula : | C8H14O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | UPQZOUHVTJNGFK-UHFFFAOYSA-N |
M.W : | 174.19 | Pubchem ID : | 11857 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.75 |
Num. rotatable bonds : | 6 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 43.14 |
TPSA : | 52.6 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.34 cm/s |
Log Po/w (iLOGP) : | 2.36 |
Log Po/w (XLOGP3) : | 1.44 |
Log Po/w (WLOGP) : | 0.75 |
Log Po/w (MLOGP) : | 0.93 |
Log Po/w (SILICOS-IT) : | 1.0 |
Consensus Log Po/w : | 1.3 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.43 |
Solubility : | 6.45 mg/ml ; 0.0371 mol/l |
Class : | Very soluble |
Log S (Ali) : | -2.15 |
Solubility : | 1.23 mg/ml ; 0.00708 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -1.27 |
Solubility : | 9.25 mg/ml ; 0.0531 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.73 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
76.55% | Stage #1: With sodium ethanolate In ethanol at 40℃; for 3 h; Stage #2: at 40 - 80℃; for 21 h; |
Sodium ethoxide (163.1g, 2mol) was added to absolute ethanol (950 mL of) and stirred until completely dissolved, diethyl methylmalonate was added dropwise at 40 degrees (174.19g, 1mol), dropwise over 1h to control ,Then continue to heat the reaction at 40 degrees 2h. Then iodomethane at 40 °C (184.5g, 1.3mol),Drop within 1h control. After warming to 80 degrees, holding 20h reflux. Stop heating, vacuum distillation of all ethanol, and then to the residue by adding 800ml of distilled water to dissolve. After the solution was extracted twice with 2 * 800 ml of ethyl acetate,The combined ethyl acetate layers were dried over anhydrous sodium sulfate, filtered with suction, and the ethyl acetate was concentrated.145.68 g of a light yellow oil was obtained. Crude purity 98.9percent, yield 76.55percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | Stage #1: With sodium methylate In methanol at 0 - 20℃; for 0.333333 h; Stage #2: for 3 h; Stage #3: With acetic acid In water |
Example 41 Synthesis of 2,5-dimethyl-4,6-dihydroxy-pyrimidine A single-necked flask containing 40 ml of methanol, placed under a nitrogen atmosphere, is cooled down to 0° C. with an ice bath, 9.72 g of sodium methylate (i.e. a solution of concentration c=3 mol.l-) is added to the reaction mixture then 5 g (53 mmoles) of acetamidine hydrochloride is added at 0° C. and in small quantities. Stirring is maintained at ambient temperature for about twenty minutes, then 8.3 ml of diethyl methylmalonate is added dropwise. Stirring is maintained for 3 hours. Then the methanol is condensed under reduced pressure (2 kPa). The crude product obtained is taken up in a minimum amount of water, followed by cooling down to 0° C. then acidifying with pure acetic acid to a pH of between 4 and 5. The white precipitate formed is filtered and rinsed with water, ethyl ether and pentane. Then the white product is dried over P2O5 under reduced pressure (0.2 kPa). 3.3 g (Yield=49percent) of expected product is obtained. TLC: Rf=0.2 (Silicagel, eluent: dichloromethane-methanol-water-acetic acid 85-15-2-2).1H-NMR (DMSOd6): ? 1.68 (s, 3H, OH-CH?C-CH3); 2.18 (s, 3H, N?C-CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.9 g | Stage #1: With sodium hydride In dimethyl sulfoxide at 20℃; for 1.5 h; Stage #2: at 100℃; for 5 h; Stage #3: With hydrogenchloride; tin In ethanol; water for 2 h; Reflux |
Sodium hydride (3.9 g) was suspended in dimethyl sulfoxide (24 mL), and diethyl methyl malonate (16 mL) was added at 0°C, and then the reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was heated to 100°C, and a solution of 2,5-dibromonitrobenzene (15.3 g) in dimethyl sulfoxide (17 mL) was added at 100°C, and then the reaction mixture was stirred at 100°C for 5 hours. The reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethanol (75 mL), and tin (11.5 g) was added at room temperature. Concentrated hydrochloric acid (45 mL) was added at 0°C, and then the reaction mixture was heated at reflux for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (4.9 g) as a brown solid. 1H-NMR (400 MHz, CDCl3) δ: 8.48 (1H, brs), 7.17 (1H, dd, J= 7.9, 1.3 Hz), 7.08 (1H, d, J = 7.9 Hz), 7.07 (1H, s), 3.41 (1H, q, J = 7.8 Hz), 1.48 (3H, d, J = 7.8 Hz). ESI-MS found: 226 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | at 220 - 270℃; | General procedure: A mixture of the appropriate aniline (100mmol) and substituted diethyl malonate (102mmol) was heated in a flask equipped with distillation head on a metal bath at 220–230°C for 1h and then at 260–270°C until the distillation of ethanol stopped (3–6h). With the exception of preparation of 1f, l, m, the hot liquid reaction mixture was carefully poured into stirred toluene (50mL), cooled down to room temperature and the precipitate was collected by filtration. In the case of 1f, l, m, the hot reaction mixture solidified and it was cooled down to room temperature. The above precipitate or solidified material was mixed with aqueous sodium hydroxide solution (0.5M, 250mL) and toluene (50mL). The substance that remained undissolved (in the preparation of 1c and 1m) was removed by filtration, purified by recrystallization and identified as propanediamide derivatives (1c′ and 1m′, respectively). The layers of the filtrate were separated and the aqueous layer was washed with toluene (2×40mL). The water layer was treated with decolorizing charcoal, filtered and then acidified with 10percent HCl to Congo red. The precipitated hydroxyquinolone 1 was collected by filtration, washed with water, and if necessary, purified by recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | Stage #1: at 20℃; Stage #2: With hydrogenchloride In waterAcidic aqueous solution |
Synthesis of 2-Methyl-malonic acid monomethyl ester KOH (386 mg, 6.88 mmol) was added to a solution 2-methyl-malonic acid diethyl ester (1 g, 5.74 mmol) in methanol (7 mL). The resulting mixture was stirred overnight at ambient temperature then concentrated. The resulting residue was diluted with water, acidified with conc. HCl and the product was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford 360 mg (47percent) of 2-methyl-malonic acid monomethyl ester |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With titanium(IV) isopropylate; N-fluorobis(methanesulfonyl)imide In 1,2-dichloro-ethane at 20℃; for 12 h; | Test tube equipped with a stir bar N- fluoro bis (methanesulfonyl) imide (38.2 mg, 0.2 mmol) and 1,2 g of dichloroethane (1.0 mL), at room temperature, and dissolved.Then, the same solution of 2-methylmalonic acid diethyl (17.4 mg, 0.1 mmol) and tetra -iso- propoxy orthotitanate (0.016 mL, 0.05 mmol) was added and subjected to room temperature, 12 hours .After completion of the reaction, addition of water, dichloromethane extraction (3 times), the combined organic layers washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to give a crude product. The resulting crude product was used hexafluorobenzene as internal standard in 19F-NMR measurement, 2-fluoro-2-methyl-diethyl malonate quantitatively the desired product was produced.Then purified by silica gel column chromatography (ethyl acetate / hexane = 10/90 vol / vol) ,to obtain purified 2-fluoro-2-methyl-malonic acid diethyl (7) as a colorless transparent liquid (18.7 mg, 0 .097mmol, 97percent yield). |
82% | Stage #1: With sodium hydride In tetrahydrofuran; paraffin oil at 0 - 20℃; for 1.25 h; Stage #2: With N-fluorobenzene sulfonamide In tetrahydrofuran; paraffin oil at 0 - 20℃; for 4.5 h; |
To a THF (0.5 M) solution of diethyl methylmalonate (1 eq.) was added sodium hydride (1.4 eq., 60percent (w/w) dispersion in paraffin oil) in four equal portions, three to five minutes apart. The reaction was maintained at 0°C for 15 min, before it was allowed to warm to RT over 30 min. After another 30 min of stirring at RT, the mixture was re-cooled to 0°C and then added N-fluorobenzenesulfonamide (1.1 eq.) in four equal portions. Stirring was continued at 0°C for 30 min and then at RT for 4 h, at which time it was determined to be >95percent complete by lH NMR. The reaction was then diluted with hexanes and vacuum filtered. The filter cake was washed further with hexanes and the product-containing filtrate was concentrated. More hexanes were added to induce further precipitation of the unwanted- by-products and the resulting suspension was filtered again. The filtrate thus obtained was then concentrated in vacuo to furnish a biphasic oil. The upper layer was determined to be paraffin oil and was discarded. The lower layer was the desired product (82percent yield). |
18 %Spectr. | With triethylamine pentahydrogen fluoride salt; iodosylbenzene In 1,2-dichloro-ethane at 70℃; for 24 h; | General procedure: PhIO (550 mg, 2.5 mmol), Et3N·5HF (800 mg, 4 mmol), and DCE (1 mL)were placed in a Teflon test tube. After stirring at r.t. for 15 min, the appropriate malonic ester 1 (1 mmol) and DCE (1 mL) were added. The test tube was sealed with a septum rubber and heated at 70 °C for 24 h with stirring. The reaction mixture was neutralized with aq NaHCO3 and the product was extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were washed with brine (20 mL), dried (Na2SO4), and concentrated under reduced pressure. The product was purified by column chromatography on silica gel with hexane–CH2Cl2 as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: With sodium hydride In tetrahydrofuran; paraffin oil at 0 - 20℃; for 0.75 h; Stage #2: at 0 - 20℃; for 4.5 h; |
To a THF (0.5 M) solution of diethyl methylmalonate (1 eq.) was added sodium hydride (1.4 eq., 60percent (w/w) dispersion in paraffin oil) in four equal portions, three to five minutes apart. The reaction was maintained at 0°C for 15 mm, before it was allowed to warm to RT over 30 mm. After another 30 mm of stirring at RT, the mixture was re-cooled to 0°C and then added N-fluorobenzenesulfonamide (1.1 eq.) in four equal portions. Stirring was continued at 0°C for 30 mm and then at RT for 4 h, at which time it was determined to be >95percent complete by ‘H NMR. The reaction was then diluted with hexanes and vacuum filtered. The filter cake was washed further with hexanes and the product-containing filtrate was concentrated. More hexanes was added to induce further precipitation of unwanted- by-products and the suspension was filtered again. The filtrate thus obtained was then concentrated in vacuo to furnish a biphasic oil. The upper layer was determined to be paraffin oil and was discarded. The lower layer was the desired product (82percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | Stage #1: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 0.216667 h; Inert atmosphere Stage #2: at 20℃; for 0.166667 h; Inert atmosphere |
Diethyl 2-methylmalonate (4.31 mL, 25.0 mmol) was dissolved in 25 mL of anhydrous DMF. This solution was cooled to 0° C. under an atmosphere of nitrogen. Sodium hydride (1.04 g, 26 mmol, 60percent by weight in mineral oil) was slowly added to the solution. The resulting mixture was allowed to stir for 3 minutes at 0° C., and then at room temperature for 10 minutes. 2-Bromo-1-fluoro-4-nitrobenzene (5.00 g, 22.7 mmol) was quickly added and the mixture turned bright red. After stirring for 10 minutes at room temperature, the crude mixture was evaporated to dryness and then partitioned between dichloromethane and a saturated aqueous solution of sodium chloride. The layers were separated and the organic phase was washed twice with a saturated aqueous solution of sodium chloride. The organics were concentrated to yield diethyl 2-(2-bromo-4-nitrophenyl)-2-methylmalonate (8.4 g, 99percent) as a pale yellow oil which was used without further purification. Retention time 1.86 min. |
[ 5471-77-2 ]
3-Ethoxy-2,2-dimethyl-3-oxopropanoic acid
Similarity: 0.96
[ 20605-01-0 ]
Diethyl 2,2-bis(hydroxymethyl)malonate
Similarity: 0.96
[ 80370-42-9 ]
Ethyl 2-formyl-3-oxopropanoate
Similarity: 0.96
[ 14002-73-4 ]
Ethyl 3-hydroxy-2,2-dimethylpropanoate
Similarity: 0.92
[ 5471-77-2 ]
3-Ethoxy-2,2-dimethyl-3-oxopropanoic acid
Similarity: 0.96
[ 20605-01-0 ]
Diethyl 2,2-bis(hydroxymethyl)malonate
Similarity: 0.96
[ 80370-42-9 ]
Ethyl 2-formyl-3-oxopropanoate
Similarity: 0.96
[ 14002-73-4 ]
Ethyl 3-hydroxy-2,2-dimethylpropanoate
Similarity: 0.92