* 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.
General procedure: A mixture of thienopyrimidinone (0.01 mol), POCl3 (11 mL) and PCl5 (1.5 g) was quickly heated to 105° C and boiled for 5–6 h. The solvent was evaporated. Dry product was dissolved in methylene chloride (12 mL) and neutralized by cold solution of NaOH (0.5 N). The organic phase was separated and dried over Na2SO4, filtered, and then solvent was evaporated in vacuum. The residue was crystallized from isopropyl alcohol. Yield 80percent
Reference:
[1] Pharmaceutical Chemistry Journal, 1987, vol. 21, # 2, p. 126 - 129[2] Khimiko-Farmatsevticheskii Zhurnal, 1987, vol. 21, # 2, p. 197 - 200
[3] European Journal of Medicinal Chemistry, 2016, vol. 115, p. 148 - 160
[4] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 2, p. 305 - 308
[5] European Journal of Medicinal Chemistry, 2011, vol. 46, # 3, p. 870 - 876
2
[ 4815-32-1 ]
[ 106691-21-8 ]
Reference:
[1] Pharmaceutical Chemistry Journal, 1987, vol. 21, # 2, p. 126 - 129[2] Khimiko-Farmatsevticheskii Zhurnal, 1987, vol. 21, # 2, p. 197 - 200
[3] European Journal of Medicinal Chemistry, 2011, vol. 46, # 3, p. 870 - 876
[4] European Journal of Medicinal Chemistry, 2016, vol. 115, p. 148 - 160
3
[ 106691-21-8 ]
[ 439692-69-0 ]
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 2, p. 305 - 308
With phosphorus pentachloride; trichlorophosphate; at 105℃;
General procedure: A mixture of thienopyrimidinone (0.01 mol), POCl3 (11 mL) and PCl5 (1.5 g) was quickly heated to 105 C and boiled for 5-6 h. The solvent was evaporated. Dry product was dissolved in methylene chloride (12 mL) and neutralized by cold solution of NaOH (0.5 N). The organic phase was separated and dried over Na2SO4, filtered, and then solvent was evaporated in vacuum. The residue was crystallized from isopropyl alcohol. Yield 80%
With phosphorus pentachloride; trichlorophosphate;
General procedure: A mixture of 0.33 mol thieno[2,3-d]pyrimidin-4(3H)-one, 333 mL POCl3 and 0.33 mol PCl5 was boiled until a homogeneous solution was formed. POCl3 was distilled off in vacuum and equal volume of chloroform was slowly added into the warm mixture and pH was adjusted to 7 with 10% aqueous NaOH. The organic phase was separated and dried over Na2SO4, filtered, and then solvent was evaporated in vacuum. The residue was crystallized from isopropyl alcohol or hexane. The yield of this product was 80%.
6-methyl-4-[(3-phenylisoxazol-5-yl)methoxy]thieno[2,3-d]pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
With triethylamine; In isopropyl alcohol; at 0 - 20℃;
General procedure: (0.184 g,1 mmol) was added into a 25 mL one-necked round-bottom flask with 5mL of dry iso-PrOH, and the mixture was stirred in a cold bath. Then a solution of Et3N (0.101 g, 1 mmol) and <strong>[90924-12-2](3-phenyl-isoxazole-5-yl)-methanol</strong> (0.175 g, 1 mmol) in 10mL dry iso-PrOH was slowly added to the reaction system using a syringe. The mixture was stirred in a cold bath for an additional 30 min, and then tem-perature was allowed to reach room temperature. After reaction completion (monitored by thin layer chromatography, TLC), the reaction mixture was evaporated under reduced pressure, and the residue was purified by column chromatog-raphy on silica gel using petroleum ether and ethyl acetate (V/V, 5:1?2:1) as eluant. Fractions with similar Rf values were combined to obtain the target compound 3a.
6-methyl-4-[3-(2-chlorophenyl)-isoxazol-5-yl]-methoxy}-thieno[2,3-d]pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
With triethylamine In isopropyl alcohol at 0 - 20℃;
2.2.1. General Synthesis of 3a: 6-methyl-4-chloro-thieno[2,3-d]pyrimidine
General procedure: (0.184 g,1 mmol) was added into a 25 mL one-necked round-bottom flask with 5mL of dry iso-PrOH, and the mixture was stirred in a cold bath. Then a solution of Et3N (0.101 g, 1 mmol) and (3-phenyl-isoxazole-5-yl)-methanol (0.175 g, 1 mmol) in 10mL dry iso-PrOH was slowly added to the reaction system using a syringe. The mixture was stirred in a cold bath for an additional 30 min, and then tem-perature was allowed to reach room temperature. After reaction completion (monitored by thin layer chromatography, TLC), the reaction mixture was evaporated under reduced pressure, and the residue was purified by column chromatog-raphy on silica gel using petroleum ether and ethyl acetate (V/V, 5:1→2:1) as eluant. Fractions with similar Rf values were combined to obtain the target compound 3a.
6-methyl-4-[3-(4-chlorophenyl)-isoxazol-5-yl]-methoxy}-thieno[2,3-d]pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
With triethylamine In isopropyl alcohol at 0 - 20℃;
2.2.1. General Synthesis of 3a: 6-methyl-4-chloro-thieno[2,3-d]pyrimidine
General procedure: (0.184 g,1 mmol) was added into a 25 mL one-necked round-bottom flask with 5mL of dry iso-PrOH, and the mixture was stirred in a cold bath. Then a solution of Et3N (0.101 g, 1 mmol) and (3-phenyl-isoxazole-5-yl)-methanol (0.175 g, 1 mmol) in 10mL dry iso-PrOH was slowly added to the reaction system using a syringe. The mixture was stirred in a cold bath for an additional 30 min, and then tem-perature was allowed to reach room temperature. After reaction completion (monitored by thin layer chromatography, TLC), the reaction mixture was evaporated under reduced pressure, and the residue was purified by column chromatog-raphy on silica gel using petroleum ether and ethyl acetate (V/V, 5:1→2:1) as eluant. Fractions with similar Rf values were combined to obtain the target compound 3a.
6-methyl-4-[3-(4-bromophenyl)-isoxazol-5-yl]-methoxy}-thieno[2,3-d]pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
With triethylamine; In isopropyl alcohol; at 0 - 20℃;
General procedure: (0.184 g,1 mmol) was added into a 25 mL one-necked round-bottom flask with 5mL of dry iso-PrOH, and the mixture was stirred in a cold bath. Then a solution of Et3N (0.101 g, 1 mmol) and (3-phenyl-isoxazole-5-yl)-methanol (0.175 g, 1 mmol) in 10mL dry iso-PrOH was slowly added to the reaction system using a syringe. The mixture was stirred in a cold bath for an additional 30 min, and then tem-perature was allowed to reach room temperature. After reaction completion (monitored by thin layer chromatography, TLC), the reaction mixture was evaporated under reduced pressure, and the residue was purified by column chromatog-raphy on silica gel using petroleum ether and ethyl acetate (V/V, 5:1?2:1) as eluant. Fractions with similar Rf values were combined to obtain the target compound 3a.