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CAS No. : | 6296-99-7 | MDL No. : | MFCD01075695 |
Formula : | C8H13NO4 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | WDTWMEZMHUEZKH-UHFFFAOYSA-N |
M.W : | 187.19 | Pubchem ID : | 226751 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | |
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 |
---|---|---|
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). |
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