反応 #41070

反応方程式

1-(4-chloro-butyl)-5-(2,4-dimethyl-oxazol-5-yl)-1H-pyrimidine-2,4-dione

(1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane

DIPEA

HCl

dioxane

→

title compound

収率 24.0%

5-(2,4-dimethyl-1,3-oxazol-5-yl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2,4(1H,3H)-pyrimidinedione hydrochloride

収率 24.0%

溶媒

EtOH

反応条件

後処理

1. 1
   その他irradiated at 130° C. for 3 hours
2. 2
   その他The solvent was removed under vacuum
3. 3
   その他the residue was partitioned between water and ethyl acetate
4. 4
   その他The organic phase was evaporated
5. 5
   workup.DISSOLUTIONthe crude dissolved in dichloromethane
6. 6
   workup.ADDITIONtreated with PS-isocyanate resin (400 mg)
7. 7
   ろ過After filtration
8. 8
   その他the solvent was evaporated
9. 9
   その他the crude purified by preparative LC-MS
10. 10
    洗浄eluting with MeOH
11. 11
    その他the product obtained

実験手順

A solution of 1-(4-chloro-butyl)-5-(2,4-dimethyl-oxazol-5-yl)-1H-pyrimidine-2,4-dione (Prep65, 100 mg, 0.34 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 68 mg, 0.3 mmol), and DIPEA (130 mg, 1 mmol) in absolute EtOH (3 ml) was placed in a microwave oven and irradiated at 130° C. for 3 hours. The solvent was removed under vacuum and the residue was partitioned between water and ethyl acetate. The organic phase was evaporated, the crude dissolved in dichloromethane and treated with PS-isocyanate resin (400 mg) under stirring for 3 h. After filtration, the solvent was evaporated and the crude purified by preparative LC-MS. The residue was loaded over a SCX cartridge eluting with MeOH and the product obtained was treated with 4N HCl in dioxane (1 eq), to give the title compound as a white powder. (43 mg, 24% yield).

出典