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 19669노트

반응식

HRID 19669 반응식
[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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-02dcb318d6b7438f8b6fdc5f271a3bc7
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745458B2

반응 노트

불러오는 중…