Potassium Fluoride → 5-(5-chloro-2-fluoro-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride

HRID 12793

反応式

HRID 12793 の反応式
I[C:2]1[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][C@H:15]3[C@:13]([C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=4)([CH2:14]3)[CH2:12]2)[CH:7]=1.[F:29][C:30]1[C:35](B(O)O)=[CH:34][C:33]([Cl:39])=[CH:32][N:31]=1.[F-].[K+]>CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[ClH:39].[ClH:39].[Cl:39][C:33]1[CH:34]=[C:35]([C:2]2[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]3[CH2:16][C@H:15]4[C@:13]([C:17]5[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=5)([CH2:14]4)[CH2:12]3)[CH:7]=2)[C:30]([F:29])=[N:31][CH:32]=1

参加物

6

反応物 3

HCID 522689Potassium FluorideHCID 249017795-Chloro-2-fluoropyridine-3-boronic AcidHCID 675197195-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

生成物 1

HCID 866159605-(5-chloro-2-fluoro-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride収率 6%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 887Methanol溶媒

反応条件

温度
120 °C

実験手順

A mixture of 5-iodo-1-{3-[(1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hex-3-yl]-propyl}-1H-pyrimidine-2,4-dione (Prep 40, 150 mg, 0.3 mmol), 2-fluoro-5-chloropyridine-3-boronic acid (142 mg, 0.9 mmol), KF (157 mg, 2.7 mmol), and Pd(OAc)2 (20 mg) in degassed MeOH (4 ml) was placed in a microwave oven and warmed at 120° C. for 25 minutes. The mixture was filtered, MeOH was evaporated and the crude partitioned between brine and ethyl acetate. The organic phase was dried (Na2SO4) and evaporated; the crude was purified by flash chromatography with ethyl acetate-NH4OH (0.5%) to give the title compound (10 mg, 6% yield).

後処理

  1. customwas placed in a microwave oven
  2. filtrationThe mixture was filtered
  3. customMeOH was evaporated
  4. customthe crude partitioned between brine and ethyl acetate
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. customevaporated
  7. customthe crude was purified by flash chromatography with ethyl acetate-NH4OH (0.5%)

出典と根拠

ORDレコード
ord-2f63d5a76ab14a41b250ef46922cb2d2
出典データセット
uspto-grants-2010_06
特許番号
US07727988B2

関連ノート

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