Diisopropylethylamine → 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

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).

1. customThe mixture was placed in a microwave oven
2. customirradiated at 150° C. for 6 hours (3 cycles×1 h)
3. additionThe two mixtures were mixed
4. customevaporated under vacuum
5. dissolutionThe residue was dissolved in ethyl acetate
6. washwashed with water
7. customThe crude was purified by preparative LC-MS

ORD 기록

ord-180b5e24272947e2bce6c6597ec2e050

출처 데이터셋

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07727988B2