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

Reaction equation

HRID 12793 reaction equation
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

Participants

6

Reactant 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

Product 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 dihydrochlorideYield 6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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%)

Sources & evidence

ORD record
ord-2f63d5a76ab14a41b250ef46922cb2d2
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Linked notes

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