Diisopropylethylamine → 5-(6-methyl-2-pyridinyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride

HRID 12780노트

반응식

HRID 12780 반응식
[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[N:13]=2)[C:9](=[O:19])[NH:8][C:7]1=[O:20].[F:21][C:22]([F:36])([F:35])[C:23]1[CH:28]=[CH:27][C:26]([C@:29]23[CH2:34][C@H:33]2[CH2:32][NH:31][CH2:30]3)=[CH:25][CH:24]=1.CCN(C(C)C)C(C)C>CCO>[ClH:1].[ClH:1].[CH3:18][C:14]1[N:13]=[C:12]([C:10]2[C:9](=[O:19])[NH:8][C:7](=[O:20])[N:6]([CH2:5][CH2:4][CH2:3][CH2:2][N:31]3[CH2:32][C@H:33]4[C@:29]([C:26]5[CH:25]=[CH:24][C:23]([C:22]([F:21])([F:36])[F:35])=[CH:28][CH:27]=5)([CH2:34]4)[CH2:30]3)[CH:11]=2)[CH:17]=[CH:16][CH:15]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 589942001-(4-Chloro-butyl)-5-(6-methyl-pyridin-2-yl)-1H-pyrimidine-2,4-dioneHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

생성물 1

HCID 686915305-(6-methyl-2-pyridinyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

A solution of 1-(4-chloro-butyl)-5-(6-methyl-pyridin-2-yl)-1H-pyrimidine-2,4-dione (Prep51, 95 mg, 0.32 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 74 mg, 0.32 mmol), and TEA (98 μl, 1 mmol) in absolute EtOH (4 mL) was refluxed for 48 h. Then dry DIPEA (83.6 mg, 0.64 mmol) was added and the mixture placed in a microwave oven and irradiated at 125° C. for 4 hours. The solvent was removed under vacuum and the residue was partitioned between water and ethyl acetate. The organic phase was dried (Na2SO4), filtered and evaporated. The residue was dissolved in DCM and treated with PS-isocyanate resin (250 mg) under stirring for 2 h. After filtration and evaporation of the solvent, the crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2) to give the title compound as free base.

후처리

  1. customthe mixture placed in a microwave oven
  2. customirradiated at 125° C. for 4 hours
  3. customThe solvent was removed under vacuum
  4. customthe residue was partitioned between water and ethyl acetate
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in DCM
  9. additiontreated with PS-isocyanate resin (250 mg)
  10. filtrationAfter filtration and evaporation of the solvent
  11. customthe crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2)

출처 및 근거

ORD 기록
ord-c1f25d7c76c845f38c8ea757d242b0f0
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727988B2

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