Ethanol → 5-(2-methyl-3-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 12776ノート

反応式

HRID 12776 の反応式
[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[CH:11]=[C:10](C2(C)C=CC=CN2)[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.CC[N:39]([CH:43]([CH3:45])[CH3:44])[CH:40]([CH3:42])C.[CH3:46]CO>>[ClH:1].[ClH:1].[CH3:45][C:43]1[C:44]([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:35])[F:36])=[CH:28][CH:27]=5)([CH2:34]4)[CH2:30]3)[CH:11]=2)=[CH:46][CH:42]=[CH:40][N:39]=1

参加物

5

反応物 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 686953191-(4-chloro-butyl)-5-(2-methyl-pyridin-2-yl)-1H-pyrimidine-2,4-dione

生成物 1

HCID 686908255-(2-methyl-3-pyridinyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride収率 36%

実験手順

A solution of 1-(4-chloro-butyl)-5-(2-methyl-pyridin-2-yl)-1H-pyrimidine-2,4-dione (Prep48, 100 mg, 0.34 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 77 mg, 0.34 mmol), and DIPEA (132 μl, 1 mmol) in absolute EtOH (3 mL) was heated at 125° C. for 3 hours in a microwave oven. 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 3 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 (60 mg, 36% yield) as free base.

後処理

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

出典と根拠

ORDレコード
ord-8fb00b688f9142ad93c4feb8cbde5bf8
出典データセット
uspto-grants-2010_06
特許番号
US07727988B2

反応ノート

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