* 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.
With potassium carbonate; In N-methyl-acetamide; water;
(i) 4,6-Dihydroxy-5-benzylthiopyrimidine Benzylmercaptan (6 ml, 0.05 mole) was added to a stirred and heated (90) suspension of <strong>[15726-38-2]5-bromo-4,6-dihydroxypyrimidine</strong> (9.5 g, 0.05 mole) and potassium carbonate (7.5 g, 0.055 mole) in dimethylformamide (25 ml). The reaction mixture was stirred and heated at 95-105 C. under an atmosphere of dry nitrogen for 3.5 hours. The mixture was poured into ice cold water (400 ml) with vigorous stirring and then acidified to pH 1 with hydrochloric acid. After stirring for 0.5 hours the suspension was filtered and the solid which was collected was rinsed several times with n-hexane and diethyl ether. The remaining brown solid was air dried to give 4,6-dihydroxy-5-benzylthiopyrimidine (5.5 g 50%) PMR spectrum: (d6 DMSO) 3.96 (S, 2h); 7.2 (bm, 5H); 8.11 (s, 1H); 12.2 (bs, 2H).
50%
With potassium carbonate; In N-methyl-acetamide; water;
(i) 4,6-Dihydroxy-5-benzylthiopyrimidine Benzylmercaptan (6 ml, 0.05 mole) was added to a stirred and heated (90) suspension of 5-bromo- 4,6-dihydroxypyrimidine (9.5g, 0.05 mole) and potassium carbonate (7.5g, 0.055 mole) in dimethylformamide (25 ml). The reaction mixture was stirred and heated at 95-105C under an atmosphere of dry nitrogen for 3.5 hours. The mixture was poured into ice cold water (400 ml) with vigorous stirring and then acidified to pH 1 with hydrochloric acid. After stirring for 0.5 hours the suspension was filtered and the solid which was collected was rinsed several times with n-hexane and diethyl ether. The remaining brown solid was air dried to give 4,6-dihydroxy-5-benzylthiopyrimidine (5.5g 50%) PMR spectrum: (d6 DMSO) 3.96 (S, 2h); 7.2 (bm, 5H); 8.11 (s, 1H); 12.2 (bs, 2H).
Reference Example 2 Production of 5-bromo-pyrimidine-4,6-diol In 25 ml of glacial acetic acid was dissolved 15 g of dihydropyridine-4,6-dione and the resulting solution was heated to 70C. A solution of 23.3 g of bromine in 50 ml of glacial acetic acid was slowly dropped thereinto. The reaction solution was cooled to room temperature and allowed to stand overnight. After standing, the precipitated crystals were collected by filtration. These crude crystals were recrystallized from water to obtain 14.5 g of 5-bromo-pyrimidine-4,6-diol as orange crystals.
4,6-dichloro-5-(2-chlorophenylsulfanyl)-pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In N-methyl-acetamide;
Example 18 Production of 4,6-dichloro-5-(2-chlorophenylsulfanyl)-pyrimidine In 5 ml of dimethylformamide was suspended 249 mg of sodium hydride (a 60% oil dispersion). Thereto was added 628 mg of 2-chlorothiophenol. The resulting mixture was stirred at room temperature for 1 hour to obtain solution 1. On the other hand, 1.0 g of 5-bromopyrimidine-4,6-diol was dissolved in 5 ml of dimethylformamide to obtain solution 2. Solution 1 was added dropwise to solution 2. The resulting mixture was heated under reflux for 8 hours, cooled to room temperature, and then poured into ice water. The crystals precipitated were collected by filtration, washed with water and then dried. Subsequently, the crystals were dissolved in 3 ml of phosphorus oxycloride and the resulting solution was heated under reflux for 2 hours. The reaction solution was cooled to room temperature and then poured into ice water. The resulting mixture was made basic with aqueous ammonia and extracted with toluene. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. The drying agent was removed and the solvent was distilled off under reduced pressure to obtain 453 mg of 4,6-dichloro-5-(2-chlorophenyl)sulfanylpyrimidine as yellow crystals.
Example 14 Production of 4,6-dichloro-5-phenylsulfanylpyrimidine In 5 ml of dimethylformamide was suspended 207 mg of sodium hydride (a 60% oil dispersion). Thereto was added 628 mg of thiophenol. The resulting mixture was stirred at room temperature for 1 hour to obtain solution 1. On the other hand, 1.0 g of 5-bromopyrimidine-4,6-diol was dissolved in 5 ml of dimethylformamide to obtain solution 2. Solution 1 was added dropwise to solution 2. The resulting mixture was stirred at room temperature for 3 hours and then poured into ice water. The precipitated crystals were collected by filtration and dried. Then, the crystals were dissolved in 3 ml of phosphorus oxychloride and the resulting solution was heated under reflux. The reaction solution was cooled to room temperature and poured into ice water. The resulting mixture was made basic with aqueous ammonia and extracted with methylene chloride. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. The drying agent was removed and the solvent was distilled off under reduced pressure to obtain crude crystals. The crude crystals were recrystallized from methanol/water to obtain 490 mg of 4,6-dichloro-5-phenylsulfanylpyrimidine as light-brown crystals.
4,6-dichloro-5-(4-chlorophenylsulfanyl)-pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In N-methyl-acetamide;
Example 16 Production of 4,6-dichloro-5-(4-chlorophenylsulfanyl)-pyrimidine In 5 ml of dimethylformamide was suspended 249 mg of sodium hydride (a 60% oil dispersion). Thereto was added 628 mg of 4-chlorothiophenol. The resulting mixture was stirred at room temperature for 1 hour to obtain solution 1. On the other hand, 1.0 g of 5-bromopyrimidine-4,6-diol was dissolved in 5 ml of dimethylformamide to obtain solution 2. Solution 1 was added dropwise to solution 2. The resulting mixture was heated under reflux for 8 hours, cooled to room temperature, and then poured into ice water. The precipitated crystals were collected by filtration, washed with water and then dried. Subsequently, the crystals were dissolved in 3 ml of phosphorus oxycloride and the resulting solution was heated under reflux for 2 hours. The reaction solution was cooled to room temperature and poured into ice water. The resulting mixture was made basic with aqueous ammonia and extracted with toluene. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. The drying agent was removed and the solvent was distilled off under reduced pressure to obtain 600 mg of 4,6-dichloro-5-(4-chlorophenyl)sulfanylpyrimidine as yellow crystals.