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CAS No. : | 53554-29-3 | MDL No. : | MFCD00023234 |
Formula : | C8H10N2O3S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HDIWKNXVBQPJCO-UHFFFAOYSA-N |
M.W : | 214.24 | Pubchem ID : | 239049 |
Synonyms : |
|
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 |
---|---|---|
99.7% | S1, methylthiourea sulfate(75.2g, 0.4mol)Add to a mass fraction of 16% NaOH (250 mL, 1.18 mol) and stir for 30 min.Then diethyl ethoxymethylenemalonate (103.4 g, 0.48 mol)Soluble in 160mL of ethanol and slowly drip into the reaction solution,After the completion of the dropwise addition, the reaction was carried out at room temperature for 10 hours, when a large amount of white solid precipitated,Pumping,Washed,Drying in vacuo gave a white solid (84.7 g, 99.7%); | |
87.6% | With sodium ethanolate; In ethanol; at 20℃; for 3h; | To a solution of 2-ethoxymethylenemalonic acid diethyl ester (59.0 g, 273 mmol) in EtOH (300 mL) was added 2-methyl-isothiourea (41.5 g, 150 mmol) in an ice-H2O bath. An EtOHic solution of EtONa (2M, 300 mL) was added dropwise maintaining the reaction temperature under 5 C. The mixture was warmed to RT and stirred for 3h. After standing overnight, the solvent was removed under reduced pressure and the residue was dissolved in H2O (800 mL) at 0 C. The solution was acidified to pH 3 with cone. HCl and the precipitate collected by filtration and air-dried to yield 4-hydroxy-2- methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester as a white solid (50.8 g, 87.6% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With thionyl chloride; at 60℃; for 3h; | Ethyl 4-hydroxy-2-methylthiopyrimidine-5-carboxylate (30 g, 140 mmol) was added to a three-vial flask.Add 20g of thionyl chloride (168mmol)The reaction was heated to 60C for 3 hours. After the reaction was complete, it was cooled to 0-5C. 100 ml of water was added and crystallized at 0-5C for 1-2 hours. The mixture was filtered and vacuum dried at 50C to give 30.1 g of white solid product. Yield 92 %, pure 99.8%, |
77% | With N,N-diethylaniline; trichlorophosphate; for 5h;Heating / reflux; | A mixture of 4-hydroxy-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester (50 g, 0.234 mmol), POC13 (110 mL, 1.17 mmol) and diethylamide (70 mL, 0.28 mmol) was refluxed for 5h. The solvent was removed under vacuum and the residue was dissolved in ice H2O and cautiously neutralized with aqueous NaHCO3. After extraction with EtOAc (3x400 mL), the organic extracts were combined, dried and concentrated to give 4-chloro-2- (methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester as a yellow solid (42 g, 77% yield). |
77% | With trichlorophosphate; In acetonitrile; for 6h;Reflux; | the ethyl 4-hydroxy-2-methylsulfanyl-5-carboxylate obtained in the step S1 (55.6 g, 0.26 mol) was added to 150 mL of acetonitrile.Stir for 25min,Slowly add 135 mL of POCl3 to the reaction solution.After the addition is completed,The reaction solution was heated to reflux for 6 h.Then the reaction solution is slightly cold,The reaction solution was concentrated and the residue was poured into an ice water mixture and stirred.Adjust the pH of the reaction solution to neutral with saturated sodium bicarbonate solution.When a large amount of white solid precipitates, suction filtration is performed.The filter cake is used in turn (135mL × 3),Anhydrous ethanol (30 mL × 3) was rinsed.Then dried in vacuo to give a white solid (47.8 g, 77%); |
40% | With trichlorophosphate; at 10 - 65℃; for 7h; | Step 2. Preparation of 4-chloro-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester (B19-2): Neat POCl3 (120 mL) was cooled to 10 C. and treated portion-wise over 4 hours with B19-1 (50 g, 232 mmol) without exceeding a temperature of 25 C. The mixture was then heated at 65 C. After 3 hours the mixture was cooled to 10 C., poured into crushed ice (350 g), treated drop-wise with water (676 mL) under vigorous stirring. The resultant solids were collected and dried under reduced pressure to provide B19-2 as a pale yellow solid. Yield: 22 g, 40%. 1H NMR (CDCl3): delta 8.95 (s, 1H), 4.44 (q, 2H), 2.62 (s, 3H) and 1.42 (t, 3H). |
With trichlorophosphate; In toluene; at 55 - 105℃; for 4h; | The wet solid obtained in step-a) was dissolved in toluene (800 ml) by heating the reaction mixture to 85-90C. The reaction mixture was kept aside for 15 minutes and both the organic and aqueous layers were separated. The organic layer was heated to 110-115C to remove water from it. Cooled the reaction mixture to 55-60C. Phosphoryl chloride (106.36 g) was added to the organic layer at 55-60C, heated the reaction mixture to 100-105C and then stirred for 4 hours. The reaction mixture was cooled to 0-5C and then quenched with water at a temperature below 40C. The reaction mixture was heated to 40-45 C and separated both the organic and aqueous layers. The organic layer was washed with 5% sodium carbonate solution followed by water. The organic layer containing the title compound is taken to the next step. |
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