Preparation and application background and overview of 1-cyclopropyl-1,3-dihydroimidazo[4,5-C]pyridin-2-one
1-Cyclopropyl-1,3-dihydroimidazo[4,5-C]pyridine calcium carbonate-2-one is a pharmaceutical intermediate that can be used to prepare RSV inhibitors. 1-Cyclopropyl-1,3-dihydroimidazo[4,5-C]pyridin-2-one can be prepared in three steps from 4-methoxy-3-nitropyridine and cyclopropylamine as raw materials.
Preparation and application of 1-cyclopropyl-1,3-dihydroimidazo[4,5-C]pyridin-2-one
Preparation and application steps 1 of 1-cyclopropyl-1,3-dihydroimidazo[4,5-C]pyridin-2-one
Dissolve 10a1 (4g, 26mmol) (Molekula), cyclopropylamine 10a2 (4.5mL, 64.9mmol) (Avra) and N,N-diisopropylethylamine (8.9mL, 54mmol) in EtOH (15mL) The solution was refluxed for 3 hours. The reaction mixture was cooled to 0°C and the solids in suspension were collected by filtration. The solid obtained was washed with cold EtOH to provide intermediate 10a3.
[Tag:Title] Step 2
A solution of intermediate 10a3 (3.8 g, 21 mmol) and Pd/C 10% (760 mg) in EtOH (32 mL) was stirred under a hydrogen atmosphere at 50 psi for 2 h. Filter the catalyst through celite. The filtrate was evaporated under reduced pressure to obtain intermediate 10a4.
Preparation and application step 3 of 1-cyclopropyl-1,3-dihydroimidazo[4,5-C]pyridin-2-one
To a solution of intermediate 10a4 (2 g, 13.4 mmol) in ACN (40 mL) was added carbonyldiimidazole (2.2 g, 13.4 mmol) at 0°C. The mixture was stirred at room temperature for 1 h. The precipitate was collected by filtration to obtain intermediate 3a1-3, which is 1-cyclopropyl-1,3-dihydroimidazo[4,5-C]pyridin-2-one.
Preparation and application of 1-cyclopropyl-1,3-dihydroimidazo[4,5-C]pyridin-2-one
1-Cyclopropyl-1,3-dihydroimidazo[4,5-C]pyridin-2-one can be used to prepare respiratory syncytial virus (RSV) inhibitors with the following structure, the compound Exhibits inhibitory activity against RSV replication. Since no effective therapy for RSV infection exists, and because of the significance of RSV incidence and/or the ethics of the population at risk, the introduction of effective RSV agents would be considered a major breakthrough in the care of these patients.
References
[1][Invented in China] CN201380080493.8 Quinazoline-based respiratory syncytial virus inhibitor
[2][China invention, China invention authorization] CN201680044547.9 Respiratory syncytial virus inhibitor
