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

HRID 12770Notes

Reaction equation

HRID 12770 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.[N:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>COCCOC.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:29]1[CH:34]=[CH:33][C:32]([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:31][CH:30]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 2734379(Pyridin-4-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

Product 1

HCID 247593375-(4-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedioneYield 32%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

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, 46 mg, 0.09 mmol) was dissolved in degassed DME-water solution (5-1, 1 mL). Pyridine 4-boronic acid (22 mg, 0.18 mmol), Na2CO3 (20 mg, 0.18 mmol), 2-(dicyclohexylphosphino)biphenyl (7 mg, 0.02 mmol) and Pd(PPh3)4 (20 mg, 0.02 mmol) were added and the mixture was placed in a microwave oven and heated at 150° for 20 minutes. The mixture was diluted with ethyl acetate, and washed with water. The organic phase was dried (Na2SO4) and evaporated; the crude was dissolved in MeOH and loaded on SCX cartridge washing with MeOH and eluting with MeOH/NH3 95:5. The residue was purified by flash chromatography with DCM-MeOH—NH4OH (99-1-0.1) to give the title compound (13 mg, 32% yield) as free base.

Workup

  1. customthe mixture was placed in a microwave oven
  2. temperatureheated at 150° for 20 minutes
  3. washwashed with water
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. dissolutionthe crude was dissolved in MeOH
  7. washwashing with MeOH
  8. washeluting with MeOH/NH3 95:5
  9. customThe residue was purified by flash chromatography with DCM-MeOH—NH4OH (99-1-0.1)

Sources & evidence

ORD record
ord-d56abf5c040d410d8e4d1de612a724b3
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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