Structure of 6296-99-7
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Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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CAS No. : | 6296-99-7 |
Formula : | C8H13NO4 |
M.W : | 187.19 |
SMILES Code : | C(OC(C(C(OCC)=O)=CN)=O)C |
MDL No. : | MFCD01075695 |
Boiling Point : | No data available |
InChI Key : | WDTWMEZMHUEZKH-UHFFFAOYSA-N |
Pubchem ID : | 226751 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 45.37 |
TPSA ? Topological Polar Surface Area: Calculated from | 78.62 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.92 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 1.02 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | -0.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 0.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 0.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 0.6 |
Log S (ESOL):? ESOL: Topological method implemented from | -1.25 |
Solubility | 10.6 mg/ml ; 0.0566 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.26 |
Solubility | 1.03 mg/ml ; 0.00549 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -0.57 |
Solubility | 49.8 mg/ml ; 0.266 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) | 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 | -6.72 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 | 4.0 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) | 2.2 |
* 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 |
---|---|---|
50% | With N-ethyl-N,N-diisopropylamine; In 1,2-dichloro-ethane; at 70℃; | Step 1: Diethyl 2-((3-phenylureido)methylene)malonate To a mixture of diethyl (aminomethylene)malonate (6.0 g, 32 mmol) and phenyl isocyanate (3.8 mL, 35 mmol) in 1,2-dichloroethane (20 mL) at rt was added N,N-diisopropylethylamine (7.2 mL, 42 mmol). The reaction mixture was then stirred at 70 C. overnight, cooled to rt, added Et2O (50 mL), and stirred for another 30 min. The resulting solid was collected by filtration, washed with ether, and dried to give the product as a white solid (4.88 g, 50%). LCMS calcd for C15H19N2O5 (M+H)+: m/z=307.1. Found: 307.2. |
50% | With N-ethyl-N,N-diisopropylamine; In 1,2-dichloro-ethane; at 70℃; | To a mixuture of diethyl (aminomethylene)malonate (6.0 g, 32 mmol) and phenyl isocyanate (3.8 mL, 35 mmol) in 1,2-dichloroethane (20 mL) at rt was added N,N- diisopropylethylamine (7.2 mL, 42 mmol). The reaction mixture was then stirred at 70 C overnight, cooled to rt, added Et^O (50 mL), and stirred for another 30 min. The resulting solid was collected by filtration, washed with ether, and dried to give the product as a white solid (4.88 g, 50%). LCMS calcd for C15H19N2O5 (M+H)+: m/z = 307.1. Found: 307.2. |
44.5% | With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100℃; for 18.0h; | To a 40 mL vial containing diethyl 2-(aminomethylene)malonate (400 rng, 2.14 mmol), DIPEA (411 uL, 2.35 mmol) in dioxane (0.6 mL) was added isocyanatobenzene (244 uL, 2.24 mmol). The reaction was heated to 100C for 18 hours then cooled to room temperature. The precipitate that formed was collected by filtration with small dioxane and hexane rinses and dried under vacuum to give the title compound (294 mg, 44.5%) as a white solid. Ti NMR (500 MHz, DMSO-de) d 10.76 - 10.50 (m, 1H), 10.48 - 10.25 (m, 1H), 8.48 (br s, 1H), 7.59 - 7.45 (m, 2H), 7.39 - 7.25 (m, 2H), 7.16 - 7.02 (m, 1H), 4.25 (q,.7=7.0 Hz, 2H), 4.16 (q,.7=7.0 Hz, 2H), 1.31 - 1.22 (ra, 6H); LCMS (M+H) = 307; HPLC RT = 2.298 min (Column: Chromolith ODS S5 4.6 x 50 mm; Mobile Phase A: 10:90 MeOH: ater with 0.1% TFA; Mobile Phase B: 90: 10 MeOH: water with 0.1% TFA; Temperature: 40 C; Gradient: 0-100% B over 4 min; Flow: 4 mL/min). |
With N-ethyl-N,N-diisopropylamine; In 1,2-dichloro-ethane; at 100℃; for 6.0h; | l-Ethyl-2,4-dioxo-3-phenyl-l,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7- dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide. To a solution of 2- aminomethylene-malonic acid diethyl ester (0.75 g, 4.0 mmol) and phenyl isocyanate (0.57 g, 4.4 mmol) in 1 ,2-dichloroethane (20 mL) was added N,N-diisopropylethylamine (0.77 mL, 4.4 mmol) and heated at 100 C 6 h. The mixture was cooled and filtered. The solids were purified by column chromatography with 0-5% MeOH in methylene chloride. This intermediate urea was suspended in ethanol (10 mL) and 21% NaOEt in ethanol (1.29 mL, 4.0 mmol ) was added. After 18 h the solvent was removed under vacuum and the residue was slurred in ethyl acetate. The organics were washed with 1M citric acid solution, water and brine. The solvent was removed under vacuum and the residue was purified by chromatography with 0-5% MeOH in dichloromethane to give 0.50 g (40%). The ester was alkylated and hydro lyzed using methods for example 92 to give l-ethyl-2,4- dioxo-3-phenyl-l,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid. 1H NMR (DMSO) ?: 12.65 (bs, 1H), 8.82 (s, 1H), 7.54-7.43 (m, 3H), 7.32-7.29 (m, 2H), 4.02 (q, 2H, J = 7.1 Hz), 1.26 (t, 3H, J = 7.1 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In toluene; at 127℃; for 48.0h; | To a solution of cyclohexanone (4.6 ml, 44.3 mmol) in toluene (170 ml) is added 2- aminomethylene-malonic acid diethyl ester (8.3 g, 44.3 mmol) and p-toluenesulfonic acid (305 mg, 1.77 mmol). The reaction mixture is heated to 127°C for 48h in a Dean-Stark trap to remove water. The crude mixture is concentrated in vacuo and purified by MPLC (500 g silica gel, eluent cyclohexane:EtOAc 80:20 to 70:30) to give 2-(cyclohex-1 - enylaminomethylene)-malonic acid diethyl ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With ammonia; In ethanol; at 20℃; for 1.0h; | Ammonia was passed through ethanol (200 mL) for 30 minutes. Diethyl 2- (ethoxymethylene) malonate (21.6 g, 0.1 mol, 1.0 eq) was dissolved in an ammonia / ethanol solution and reacted at room temperature for 1 hour. After the reaction was detected by LC-MS and TLC, the reaction was concentrated. The crude product was purified by silica gel column chromatography (100-200 mesh silica gel, PE / EA = 5: 1) to obtain a white solid (18 g, yield: 96%) |
With ammonia; In ethanol; at 20℃; for 1.0h; | 2-Ethoxymethylene-malonic acid diethyl ester (20 ml, 100 mmol) and a 10% soln. of ammonia in EtOH (37 ml, 220 mmol) are stirred at rt for 1 h. The mixture is evaporated and dried in HV to give 2-aminomethylene-malonic acid diethyl ester that is used without further purification. | |
With ammonia; In ethanol; | a Diethyl aminomethylenemalonate To diethyl ethoxymethylenemalonate (50.13 g, 0.232 mmol), cooled to -20 C. under nitrogen, was added a 2.0 M solution of ammonia in ethanol (232 ml, 0.464 mmol) and the resulting solution was stirred at room temperature overnight. The solution was then evaporated in vacuo to give a quantitative yield of the title compound as a cream solid; 1H NMR (360 MHz, CDCl3) 5 1.28 (3H, t, J 7.1 Hz), 1.35 (3H, t, J 7.1 Hz), 4.19 (2H, q, J 7.1 Hz), 4.26 (2H, q, J 7.1 Hz), 5.68 (1H, br s), 8.11 (1H, dd), 8.69 (1H, br s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In ethyl acetate; toluene; | (a) To a solution of 15 g of 4H-tetrahydrothiopyran-4-one in 500 mL of toluene, 25 g of <strong>[6296-99-7]diethyl aminomethylenemalonate</strong> and 0.8 of p-toluenesulfonic acid are added. The resultant mixture is refluxed for 48 hours with a water separator under nitrogen atmosphere, then evaporated to dryness. The dried residue is purified by flash chromatography on a silica gel column, using toluene and 5percent ethyl acetate in toluene as eluents to obtain the desired product, diethyl N-(2H-5,6-dihydrothiopyran-4-yl)aminomethylenemalonate. | |
With toluene-4-sulfonic acid; In ethyl acetate; toluene; | (a) To a solution of 15 g of 4H-tetrahydrothiopyran-4-one in 500 mL of toluene, 25 g of <strong>[6296-99-7]diethyl aminomethylenemalonate</strong> and 0.8 g of p-toluenesulfonic acid are added. The resultant mixture is refluxed for 48 hours with a water separator under nitrogen atmosphere, then evaporated to dryness. The dried residue is purified by flash chromatography on a silica gel column, using toluene and 5percent ethyl acetate in toluene as eluents to obtain the desired product, diethyl N-(2H-5,6-dihydrothiopyran-4-yl)-aminomethylenemalonate. | |
With toluene-4-sulfonic acid; In ethyl acetate; toluene; | (a) To a solution of 15 g of 4H-tetrahydrothiopyran-4-one in 500 mL of toluene, 25 g of <strong>[6296-99-7]diethyl aminomethylenemalonate</strong> and 0.8 g of p-toluenesulfonic acid are added. The resultant mixture is refluxed for 48 hours with a water separator under nitrogen atmosphere, then evaporated to dryness. The dried residue is purified by flash chromatography on a silica gel column, using toluene and 5percent ethyl acetate in toluene as eluents to obtain the desired product, diethyl N-(2H-5,6-dihydrothiopyran-4-yl)aminomethylenemalonate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In toluene; at 135℃;Inert atmosphere; | EXAMPLE 136; N'-(2-Chloro-5-(4-(4-morpholinyl)-7,8-dihydro-l,6-naphthyridin-6(5H)-yl)-3- pyridinyl)-N,N-dimethylsulfamide; (1) 2-((l-(ethoxycarbonyl)-l,2,3,6-tetrahydropyridin-4- ylamino)methylene)malonate.; A mixture of 1 -carbethoxy-4-piperidone (10.0 mL, 66.3 mmol), 4-methylbenzenesulfonic acid hydrate (0.60 g, 3.15 mmol), and diethyl 2- (aminomethylene)malonate (4.65 g, 24.84 mmol) in toluene (50 mL) in a 150 mL RBF equipped with a Dean-Stark trap was heated to 135 0C under nitrogen overnight. The reaction mixture was cooled and concentrated. The oil was purified on silica gel using acetone-hexane (1 :9-4:6). The <n="166"/>product fraction was collected and concentrated to yellow oil that was contaminated by the ketone starting material. This material was used directly in the next step. [00435] 1H NMR (400 MHz, CHLOROFORM-tf) delta ppm 1.22 - 1.41 (m, 9 H) 2.35 (br. s., 2 H) 3.68 (t, J=5.58 Hz, 2 H) 4.06 (d, J=1.76 Hz, 2 H) 4.11 - 4.32 (m, 6 H) 5.33 - 5.43 (m, 1 H) 8.14 (d, J=13.89 Hz, 1 H) 10.60 (br. s., 1 H) |
Tags: 6296-99-7 synthesis path| 6296-99-7 SDS| 6296-99-7 COA| 6296-99-7 purity| 6296-99-7 application| 6296-99-7 NMR| 6296-99-7 COA| 6296-99-7 structure
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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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