2,4-Dichlorothieno[2,3-d]pyrimidine

Thieno[2, 3-d]pyrimidine-2, 4(1H, 3H)-dione (12) (2.5 g, 0.012 mol) and a drop of DMF were added to 20 mL POClTo 1 g of dry thieno [2, 3-d] pyrimidine-2, 4 (1H, 3H) -dione was added 10 g of phosphorus oxychloride, Add 1 drop of DMF catalyst, heating to 115 , the reaction 5h, the reaction is completed, the reaction slowly added to the crushed ice, While stirring vigorously, A brown solid, Filter, filter residue dissolved in 50mL of dichloromethane, to the solution by adding 1g activated carbon and 2g silica gel, Heated to 45 reflux decolorization 1h, while the hot filter, remove the solvent, Pale yellow solid, 2, 4-dichlorothieno [2, 3-d] pyrimidine in a yield of 56.0percent.Thieno[2, 3-d] pyrimidine-2, 4 (1H, 3H) -dione (IX-2) (5.0 g, 29.7 mmol)And 3 mL of N, N-dimethylaniline were dissolved in 30 mL of acetonitrile, It was cooled to 0 ° C.16 mL of phosphorus oxychloride is kept at the reaction temperature not higher than 25 ° C.I am dripping slowly. The reaction mixture was heated and stirred at 80-85 ° C. for 24 hours.The reaction solution was cooled to 15 ° C., Was slowly added to 70 mL of ice water.The obtained slurry was collected by filtration, And washed with cold water (20 mL).After drying, column chromatography (elution solvent: hexane: dichloroMethane = 1: 2)3.41 g (yield 56percent) of the dichloro compound (IIa-2) was obtained as gray crystals.3 g (0.018 mol) of the intermediate lib was placed in a 100 mL three-necked flask, 30 mL (0.329 mol) of phosphorus oxychloride was slowly added dropwise, After 30 min addition, 2 drops of DMF were added to the reaction mixture and the reaction was heated to reflux for 8 h. The reaction was poured into 1000 g of ice water with stirring, and a large amount of orange-colored solid was precipitated. The filter cake was washed with a large amount of water and dried at 45 ° C for 24 hours to obtain 1.8 g of an orange solid in a yield of 49percent.Under a nitrogen streamThieno [2, 3-d] pyrimidine-2, 4 (1H, 3H) -dione (8.4 g, 50.0 mmol) and phosphoryl chlorideL), which was stirred for 3 hours at 106 ° C. After completion of the reaction, the organic layer was separated using ethyl acetateWater was removed using MgSO4. The solvent of the organic layer was removed, and the residue was purified by column chromatography to obtain the target compound2, 4-dichlorothieno [2, 3-d] pyrimidine (4.2 g, 20.5 mmol, yield 41percent).A mixture of thieno[2, 3-φyrimidine-2, 4(l//, 3//)-dione (100 mg, 0.59 mmol) and phosphonyl chloride (2 mL, 21.5 mmol) was heated at 1 16 A total of 0.8 mL N, N-dimethylaniline was added to 3.0 g of thieno[2, 3-d]pyrimidine-2, 4-(1H, 3H)-dione 6a in 20 mL POCl (51 g, 250 mmol), 28percent aqueous ammonia (94g, 750mmol a flask containing 500mL of ethanol, The reaction was stirred for 48 hours with stirring at room temperature.TLC monitors the reaction endpoint.The precipitated solid was filtered, and the ethanol was rinsed.Drying gave Compound 22-1 (29 g, yield 63percent).General procedure: 2, 4-Dihydroxythieno[3, 2-d]pyrimidine (M1) (3.38 g, 0.020 mol) was added to the reaction flask.Phosphorus oxychloride (11.6 ml, 0.127 mol) was added.N, N-dimethylaniline (7.44 ml, 0.058 mol) was added dropwise with stirring at room temperature for 3 hours under reflux.Stop heating, Pour into 100ml of ice water.Precipitating a brownish black solid, Filtering, dry, Column chromatography (petroleum ether - ethyl acetate = 3: 1) to give a pale yellow solid 2.10g, The yield was 51.2percent.

Molecular Weight:205.06
XLogP3:3.5
Hydrogen Bond Acceptor Count:3
Exact Mass:203.9315746
Monoisotopic Mass:203.9315746
Topological Polar Surface Area:54
Heavy Atom Count:11
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes