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

HRID 12786

반응식

HRID 12786 반응식
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.[CH3:29][O:30][C:31]1[C:36](B(O)O)=[CH:35][CH:34]=[CH:33][N:32]=1.[F-].[K+]>CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:29][O:30][C:31]1[C:36]([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)=[CH:35][CH:34]=[CH:33][N:32]=1

참가 물질

6

반응물 3

HCID 522689Potassium FluorideHCID 2762709(2-Methoxypyridin-3-yl)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

생성물 1

HCID 247595505-[2-(methyloxy)-3-pyridinyl]-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 887Methanol용매2회

실험 절차

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 (Prep40, 150 mg, 0.3 mmol) was dissolved in degassed MeOH (4 mL). 2-Methoxy-pyridine-3-boronic acid (136 mg, 0.9 mmol), KF (155 mg, 2.7 mmol), and Pd(OAc)2 (15 mg, 10% weight) were added and the mixture was heated to vigorous reflux for 2.5 hours. The mixture was diluted with MeOH, loaded on SCX cartridge washing with MeOH and MeOH/NH3 95:5. The solvent was evaporated under vacuum and the residue was purified by flash chromatography with ethyl acetate to give the title compound as free base (70 mg, 48% yield).

후처리

  1. temperaturethe mixture was heated
  2. temperatureto vigorous reflux for 2.5 hours
  3. washwashing with MeOH and MeOH/NH3 95:5
  4. customThe solvent was evaporated under vacuum
  5. customthe residue was purified by flash chromatography with ethyl acetate

출처 및 근거

ORD 기록
ord-6a3ad0ac470e46af8d3f533493a1a0dd
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727988B2

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