Thionyl Chloride → 4-Chloro-N-(4-chloro-6-methoxy-5-pyrimidinyl)-3-cyanobenzamide

To a suspension of the above-mentioned 4-chloro-3-cyanobenzoic acid (1.20 g, 6.61 mmol) in dry benzene (10 mL) was added thionyl chloride (0.58 mL, 7.95 mmol). The mixture was heated under refluxing for 4 hours, and then placed under reduced pressure to distill the solvent off. To the residue was added dry dichloromethane (5 mL), and the mixture was placed under reduced pressure to distill the dry benzene and the remaining thionyl chloride off. The residue was dissolved in dry dichloromethane (45 mL). The resulting solution was dropwise added under ice-cooling to a solution of 5-amino-4-chloro-6-methoxypyrimidine (2.11 g, 13.2 mmol) in dry dichloromethane (45 mL) for 5 minutes. The mixture was stirred at room temperature for 115 hours. The precipitated crystalline product was collected by filtration, washed with dichloromethane (5 mL×2), and placed under reduced pressure to distill the solvent off. The residue was repeatedly purified by silica gel column chromatography (methanol/chloroform), to obtain 1.61 g (yield 75%) of the titled compound as a pale brown crystalline product.

1. temperatureThe mixture was heated
2. temperatureunder refluxing for 4 hours
3. distillationto distill the solvent off
4. additionTo the residue was added dry dichloromethane (5 mL)
5. distillationto distill the dry benzene
6. dissolutionThe residue was dissolved in dry dichloromethane (45 mL)
7. additionThe resulting solution was dropwise added under ice-
8. filtrationThe precipitated crystalline product was collected by filtration
9. washwashed with dichloromethane (5 mL×2)
10. distillationto distill the solvent off
11. customThe residue was repeatedly purified by silica gel column chromatography (methanol/chloroform)

ORDレコード

ord-da1e4742d2e54c9f9b0b31469db3d907

出典データセット

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07598254B2