Reaktion #41057

Reaktionsgleichung

5-Phenyl-1H-pyrimidine-2,4-dione

5-o-Tolyl-1H-pyrimidine-2,4-dione

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

Ethyl-diisopropyl-amine

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

ethyl-diisopropyl-amine

5-Phenyl-1H-pyrimidine-2,4-dione

5-o-Tolyl-1H-pyrimidine-2,4-dione

→

title compound

Ausbeute 62.5%

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

Ausbeute 62.5%

Lösungsmittel

MeCN DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was placed in a microwave oven
2. 2
   Sonstigeirradiated at 150° C. for 6 hours (3 cycles×1 h)
3. 3
   workup.ADDITIONThe two mixtures were mixed
4. 4
   Sonstigeevaporated under vacuum
5. 5
   workup.DISSOLUTIONThe residue was dissolved in ethyl acetate
6. 6
   Waschenwashed with water
7. 7
   SonstigeThe crude was purified by preparative LC-MS

Vorschrift

5-Phenyl-1H-pyrimidine-2,4-dione (Prep53, 52 mg, 0.25 mmol) was dissolved in MeCN-DMSO (3:1, 3 mL). Ethyl-diisopropyl-amine (132 μl, 0.8 mmol) and (1S,5R)-3-(3-chloro-propyl)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep13, 69 mg, 0.3 mmol) were added. The mixture was placed in a microwave oven and then irradiated at 150° C. for 6 hours (3 cycles×1 h). A second run was performed on 5-Phenyl-1H-pyrimidine-2,4-dione (Prep53, 123 mg, 0.43 mmol), ethyl-diisopropyl-amine (0.2 μl, 1.2 mmol) and (1S,5R)-3-(3-chloro-propyl)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep13, 130 mg, 0.43 mmol) in the same conditions. The two mixtures were mixed and evaporated under vacuum. The residue was dissolved in ethyl acetate and washed with water. The crude was purified by preparative LC-MS to give 79 mg of the title compound as trifluoroacetate salt. The compound was loaded on SCX cartridge washing with MeOH and then eluting with MeOH/NH3 95:5. The free base obtained was treated with 4N HCl in dioxane (2 eq), to give the title compound as a white powder (32 mg).

Quelle