反应详情

温度

200 °C

In a microwave vial, to the solution of 50 mg (0.13 mmol) 2-(6-fluoro-1H-benzo[d]imidazol-1-yl)N4—((R)-8-fluorochroman-4-yl)pyrimidine-4,5-diamine (known compound, e.g. WO 2006/108103) in 0.75 mL anhydrous acetonitrile was added 24 mg (0.32 mmol) thiourea. The vial was capped and the mixture was heated in an Emrys Optimizer microwave at 200° C. for 30 minutes. The resulting red dark suspension was concentrated in vacuo, and partitioned between water and EtOAc. Extract this aqueous phase with EtOAc three more times, and the combined organic layer was concentrated in vacuo, and purified by silica gel column chromatography eluting with DCM and MeOH to yield 8 mg (14%) the titled compound as a pale yellow solid. (Note: On similar diamines, cyclization with 1,1′-thiocarbonyl-diimidazole at 0° C., then slowly warm up to room temperature was found to give improved yields.)

1. customThe vial was capped
2. concentrationThe resulting red dark suspension was concentrated in vacuo
3. custompartitioned between water and EtOAc
4. extractionExtract this aqueous phase with EtOAc three more times
5. concentrationthe combined organic layer was concentrated in vacuo
6. custompurified by silica gel column chromatography
7. washeluting with DCM and MeOH