5-CHLORO-1,2-DIHYDRO-4-METHOXY-2-OXO-3-PYRIDINECARBONITRILE

Light Yellow Solid

3-cyano-4-methoxy-2-H-pyridone (6.0 g, 0.04 mol)45ml glacial acetic acid into 250 ml three-necked flask, Cooling to below 15 , Then 6.18 g (0.045 mol) g of sulfonyl chloride was added dropwise, Solution temperature control between 10 ~ 15 , The rate of dropping can be controlled according to the temperature change.After dripping, Stirring for half an hour, Heating up to 52 ± 2 , Insulation 50-54 reaction 4h, TLC (TLC developing agent: ethyl acetate: methanol = 9: 1) monitoring the reaction of raw materials is completed, The reaction solution was cooled to 20 ± 2 ° C, Stir for 2 hours, filter, The filter cake was washed with 58 ml of water, The wet product was dried at 80 ° C undar normal pressure for 12 hours to dry, To give 7.01 g of 3-cyano-4-methoxy-5-chloro 2- (1H) pyridone as a white powder, Yield 95.0percentTheoretical yield 7.38g.At a temperature of 0 ° C to 5 ° C, Sulfuryl chloride was slowly added dropwise to 3-cyano-4-methoxy-2 (1 H) pyridone, the temperature was not more than 5 ° C, the rate of thionyl chloride dropping was 1.5 ml / min, Raise the temperature to produce reflux, The reaction was carried out for 6 hours, and the thionyl chloride was evaporated to dryness under reduced pressure, Add 1 ml of n-hexane solid beating 1 hour, filter, dry, that is, too. Yield 92.7percentAdd in 250 ml three-necked flask5-Chloro-4-methoxy-3-cyano -2- (1H) pyridone 5.54 g, Potassium carbonate 6.22 g, DMF 120 ml, Stir evenly.Slowly add DMFdilutedDimethyl sulfate solution, Control the internal temperature at 5-15 , After the dropwise addition, the reaction was raised to 35-40 ° C for 4-6 hours, TLC to monitor the reaction to the end, Add 30ml of concentrated ammonia to quench the reaction.The reaction solution was added to 1 L of purified water, Precipitation of a large number of solid, Stir for 0.5 hours, suction filter.The filter cake was beaten twice with 200 ml of 5percent potassium carbonate solution, Filtration, TLC showed a single spot.The filter cake was dried at 55-60 ° C for 6 hours, A white solid, I.e., 5-chloro-4-methoxy-3-cyano-1-methyl -2- (1H) -pyridone, weight 4.1g, Yield 68.8percent.Add in 100ml three-necked flask5-chloro-4-methoxy-3-cyano-2- (1H) pyridone, 48percent hydrobromic acid 40 ml, Heated to 70-80 ° C dissolved, Reaction for about 1-2 hours, Generate a lot of solid, TLC monitors the reaction to the end.The reaction system was filtered, Wash the filter cake with a small amount of purified water.The filter cake was dissolved with 100 ml of a 3percent aqueous solution of potassium carbonate, And then pre-mixed with 4N hydrochloric acid to adjust the pH to 3-4, Precipitation of a large number of solid, After stirring for 0.5 hours, The filter cake was beaten with 5 ml of methanol and 50 ml of dichloromethane, After stirring for 0.5 hours, Filter cake in 55-60 blast drying, Get class white solid, That is, structural analogues E, Weight 4.3g, yield 50.4percent.Add in 250ml three-necked flask5-chloro-4-methoxy-3-cyano-2- (1H) pyridone, 48percent hydrobromic acid 150 ml, Heating reflux reaction for about 20-24 hours, Stop the reaction, this time the system is dark red solution.The reaction solution was concentrated at 90-95 ° C under reduced pressure to dryness, Add 200ml purified water beating, After stirring for 1 hour, the filtrate was filtered.Filter cake in 55-60 blast drying, Brown solid, That gimeracil, Weight 6.57 g, yield 83.2percentPurity of 99.91percent (see Figure 1), 3-cyano-4-methoxy-2-H-pyridone (6.0 g, 0.04 mol)45ml glacial acetic acid into 250 ml three-necked flask, Cooling to below 15 , Then 6.18 g (0.045 mol) g of sulfonyl chloride was added dropwise, Solution temperature control between 10 ~ 15 , The rate of dropping can be controlled according to the temperature change.After dripping, Stirring for half an hour, Heating up to 52 ± 2 , Insulation 50-54 reaction 4h, TLC (TLC developing agent: ethyl acetate: methanol = 9: 1) monitoring the reaction of raw materials is completed, The reaction solution was cooled to 20 ± 2 ° C, Stir for 2 hours, filter, The filter cake was washed with 58 ml of water, The wet product was dried at 80 ° C under normal pressure for 12 hours to dry, To give 7.01 g of 3-cyano-4-methoxy-5-chloro 2- (1H) pyridone as a white powder, Yield 95.0percentTheoretical yield 7.38g.At a temperature of 0 ° C to 5 ° C, Sulfuryl chloride was slowly added dropwise to 3-cyano-4-methoxy-2 (1 H) pyridone, the temperature was not more than 5 ° C, the rate of thionyl chloride dropping was 1.5 ml / min, Raise the temperature to produce reflux, The reaction was carried out for 6 hours, and the thionyl chloride was evaporated to dryness under reduced pressure, Add 1 ml of n-hexane solid beating 1 hour, filter, dry, that is, too. Yield 92.7percent3-cyano-4-methoxy-2-H-pyridone (6.0 g, 0.04 mol)45ml glacial acetic acid into 250 ml three-necked flask, Cooling to below 15 , Then 6.18 g (0.045 mol) g of sulfonyl chloride was added dropwise, Solution temperature control between 10 ~ 15 , The rate of dropping can be controlled according to the temperature change.After dripping, Stirring for half an hour, Heating up to 52 ± 2 , Insulation 50-54 reaction 4h, TLC (TLC developing agent: ethyl acetate: methanol = 9: 1) monitoring the reaction of raw materials is completed, The reaction solution was cooled to 20 ± 2 ° C, Stir for 2 hours, filter, The filter cake was washed with 58 ml of water, The wet product was dried at 80 ° C under normal pressure for 12 hours to dry, To give 7.01 g of 3-cyano-4-methoxy-5-chloro 2- (1H) pyridone as a white powder, Yield 95.0percentTheoretical yield 7.38g.At a temperature of 0 ° C to 5 ° C, Sulfuryl chloride was slowly added dropwise to 3-cyano-4-methoxy-2 (1 H) pyridone, the temperature was not more than 5 ° C, the rate of thionyl chloride dropping was 1.5 ml / min, Raise the temperature to produce reflux, The reaction was carried out for 6 hours, and the thionyl chloride was evaporated to dryness under reduced pressure, Add 1 ml of n-hexane solid beating 1 hour, filter, dry, that is, too. Yield 92.7percent

Intermediate in the synthesis of antitumor agent Gimeracil.

Molecular Weight:184.58
XLogP3:0.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:184.0039551
Monoisotopic Mass:184.0039551
Topological Polar Surface Area:62.1
Heavy Atom Count:12
Complexity:335
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes