Phenacyl bromide → HCID 86688586, compound

HRID 872247Notes

Reaction equation

HRID 872247 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.Br[CH2:10][C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=O.CO.O.C([O-])(=O)C.[NH4+]>C(#N)C>[Cl:1][C:2]1[N:7]=[CH:6][N:5]2[CH:10]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:8]=[C:4]2[CH:3]=1

Participants

5

Reactant 3

HCID 6259Phenacyl bromideHCID 2380124-Amino-6-chloropyrimidineHCID 86688587HCID 86688587, compound

Product 1

HCID 86688586HCID 86688586, compoundYield 38.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 100 mL round bottom flask was charged with commerically available 6-chloropyrimidin-4-amine (300 mg, 2.316 mmol) and 2-bromo-1-phenylethanone (922 mg, 4.63 mmol). The mixture was suspended in acetonitrile (23.2 mL) and the flask was fitted with a reflux condenser and heated to reflux via heating mantle. The reaction mixture was let stir overnight. After 17 hours, LCMS showed a major peak consistent with desired by mass (m/z=230 [M+H]+); (Methanol/Water/Ammonium Acetate/Phenomenex Luna C18, 30×2 mm, 3μ ES+/−). The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The crude solid was diluted with ethyl acetate and a saturated solution of sodium bicarbonate. The contents of the flask were transferred into a separatory funnel where the aqueous was extracted with ethyl acetate (×3), analyzed for product, and subsequently discarded. The combined organics were transferred into a 125 mL Erlenemyer flask and heated using a heat gun to dissolve the remaining crude. The solution was transferred back into a separatory funnel and the organic was washed with brine (×2), dried with magnesium sulfate, concentrated under reduced pressure and purified by flash chromatography: (40 g SiO2, equilibrated with hexanes, loaded with dichloromethane, initial waste: 125 mL, fraction size: 12 mL 16×100 mm, and eluted with ethyl acetate in hexanes 0% [100 mL], 10% [250 mL], 20% [1000 mL]). Collected product containing fractions to give 7-chloro-2-phenylimidazo[1,2-c]pyrimidine (206 mg, 0.897 mmol, 38.7% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 9.38 (d, J=1.3 Hz, 1H), 8.54 (d, J=0.8 Hz, 1H), 8.06-7.99 (m, 2H), 7.86 (d, J=0.8 Hz, 1H), 7.54-7.45 (m, 2H), 7.44-7.37 (m, 1H). Mass found 230 [M+H]+.

Workup

  1. customthe flask was fitted with a reflux condenser
  2. temperatureheated
  3. temperatureto reflux
  4. temperaturevia heating mantle
  5. waitAfter 17 hours
  6. concentrationconcentrated under reduced pressure
  7. additionThe crude solid was diluted with ethyl acetate
  8. customThe contents of the flask were transferred into a separatory funnel
  9. extractionwhere the aqueous was extracted with ethyl acetate (×3)
  10. temperatureheated
  11. dissolutionto dissolve the remaining crude
  12. customThe solution was transferred back into a separatory funnel
  13. washthe organic was washed with brine (×2)
  14. dry with materialdried with magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. custompurified by flash chromatography
  17. washinitial waste: 125 mL, fraction size: 12 mL 16×100 mm, and eluted with ethyl acetate in hexanes 0% [100 mL], 10% [250 mL], 20% [1000 mL])
  18. additionCollected product containing fractions

Sources & evidence

ORD record
ord-6bff03e7d91f4b0a89a36c25bd672802
Source dataset
uspto-grants-2015_03
Patent number
US08975276B2

Reaction notes

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