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

반응식

HRID 12793 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.[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

참가 물질

6

반응물 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

생성물 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 dihydrochloride수율 6%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 887Methanol용매

반응 조건

온도
120 °C

실험 절차

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).

후처리

  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%)

출처 및 근거

ORD 기록
ord-2f63d5a76ab14a41b250ef46922cb2d2
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727988B2

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