2-Methylsulfonyl-4-benzyloxy-pyrimidine → (1S,5R)-3-[3-({4-[(phenylmethyl)oxy]-2-pyrimidinyl}oxy)propyl]-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

HRID 19669ノート

反応式

HRID 19669 の反応式
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C@:9]23[CH2:14][C@H:13]2[CH2:12][N:11]([CH2:15][CH2:16][CH2:17][OH:18])[CH2:10]3)=[CH:5][CH:4]=1.CS([C:25]1[N:30]=[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:28]=[CH:27][N:26]=1)(=O)=O>CN(C=O)C>[C:33]1([CH2:32][O:31][C:29]2[CH:28]=[CH:27][N:26]=[C:25]([O:18][CH2:17][CH2:16][CH2:15][N:11]3[CH2:12][C@H:13]4[C@:9]([C:6]5[CH:5]=[CH:4][C:3]([C:2]([F:19])([F:1])[F:20])=[CH:8][CH:7]=5)([CH2:14]4)[CH2:10]3)[N:30]=2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

参加物

4

反応物 2

HCID 113575332-Methylsulfonyl-4-benzyloxy-pyrimidineHCID 593375943-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}-1-propanol

生成物 1

HCID 57856489(1S,5R)-3-[3-({4-[(phenylmethyl)oxy]-2-pyrimidinyl}oxy)propyl]-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane収率 72.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a solution of 3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}-1-propanol (P11, 144 mg) in dry DMF (1.8 mL) NaH (60% in mineral oil, 24 mg) was added at 0° C. The mixture was stirred at this temperature for 10 min, then at room temperature for 15 min. A solution of 2-(methylsulfonyl)-4-[(phenylmethyl)oxy]pyrimidine (135 mg) in dry DMF (1.1 mL) was then added. The reaction mixture was stirred at room temperature for 5 hours, then hydrolysed with water and extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by a silica SPE cartridge (5 g) eluting with dichloromethane/methanol from 100/0 to 98/2 to give the title compound as a colourless oil (171 mg).

後処理

  1. waitat room temperature for 15 min
  2. stirringThe reaction mixture was stirred at room temperature for 5 hours
  3. extractionhydrolysed with water and extracted with ethyl acetate
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by a silica SPE cartridge (5 g)
  8. washeluting with dichloromethane/methanol from 100/0 to 98/2

出典と根拠

ORDレコード
ord-02dcb318d6b7438f8b6fdc5f271a3bc7
出典データセット
uspto-grants-2010_06
特許番号
US07745458B2

反応ノート

読み込み中…