5-Bromopyrimidine → HCID 69514180, compound

HRID 858150Notes

Reaction equation

HRID 858150 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([S:13][CH:14]2[CH2:20][CH:19]3[N:21]([CH3:22])[CH:16]([CH2:17][CH2:18]3)[CH2:15]2)=[CH:9][CH:8]=1)(=O)=O.Br[C:26]1[CH:27]=[N:28][CH:29]=[N:30][CH:31]=1.[Cl-].[Li+].C[Sn](C)C.C[Sn](C)C.[F-].[K+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)C.O1CCOCC1>[CH3:22][N:21]1[CH:19]2[CH2:18][CH2:17][CH:16]1[CH2:15][CH:14]([S:13][C:10]1[CH:11]=[CH:12][C:7]([C:26]3[CH:27]=[N:28][CH:29]=[N:30][CH:31]=3)=[CH:8][CH:9]=1)[CH2:20]2

Participants

9

Reactant 5

HCID 783445-BromopyrimidineHCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 6327618HexamethylditinHCID 72415920HCID 72415920, compound

Product 1

HCID 69514180HCID 69514180, compoundYield 12.3%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 4-[(8-methyl-8-azabicylo[3.2.1]oct-3-yl)thio]phenyl trifluoromethanesulfonate (450 mg), 5-bromopyrimidine (187 mg), lithium chloride (150 mg) and tetrakis(triphenylphosphine) palladium (0) (68 mg) under nitrogen were added hexamethylditin (386 mg) and dioxane (15 ml). The mixture was heated under reflux overnight and then poured into a mixture of aqueous potassium fluoride (1.9 g in 13 ml water) and ethyl acetate (13 ml). This mixture was stirred vigorously for 2 hours, passed through a sintered funnel and the layers separated. The organic phase was washed with brine, dried (MgSO4), filtered and evaporated. The crude material was purified on an Isco CombiFlash device, followed by UV-guided LC to yield 8-methyl-3-{[4-(5-pyrimidinyl)phenyl]thio}-8-azabicyclo[3.2.1]octane (45 mg)

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux overnight
  3. custompassed through a sintered funnel
  4. customthe layers separated
  5. washThe organic phase was washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude material was purified on an Isco CombiFlash device

Sources & evidence

ORD record
ord-b530a4d3041b4663a7b23fa6fdeb47f6
Source dataset
uspto-grants-2006_12
Patent number
US07148236B2

Reaction notes

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