Triethylamine → HCID 17956316, compound

HRID 1296701Notes

Reaction equation

HRID 1296701 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[N:18]O)[CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([S:16][CH3:17])[N:11]=2)=[CH:4][CH:3]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(N(CC)CC)C>COCCOC.[Fe](Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[N:11]([C:12]([S:16][CH3:17])=[N:13][CH:14]=[CH:15]3)[N:18]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 85865895HCID 85865895, compound

Product 1

HCID 17956316HCID 17956316, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 24458Ferrous ChlorideCatalyst3×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a 0° C. solution of 1-(4-fluorophenyl)-2-[2-(methylsulfanyl)pyrimidin-4-yl]ethanone oxime (4.0 g, 14 mmol) in ethylene glycol dimethyl ether (40 mL) was added trifluoroacetic anhydride (3.0 g, 14 mmol) dropwise. The reaction was allowed to warm to 20° C., then re-cooled to 0° C. Triethylamine (2.9 g, 29 mmol) was added dropwise so that the internal reaction temperature did not exceed 10° C. The reaction was allowed to warm to room temperature and was stirred for 2 hours. Iron (II) chloride (18 mg, 0.14 mmol) was added and the mixture heated to 80° C. for 2 hours. An additional portion of iron (II) chloride (18 mg, 0.14 mmol) was added and the mixture heated at 80° C. for 2 hours. An additional portion of iron (II) chloride (18 mg, 0.14 mmol) was added and the mixture heated at 80° C. for 4 hours. The reaction was allowed to cool to room temperature and stirred overnight. The mixture was partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate (2×20 mL) and the organic layers combined. The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica chromatography eluting with 1% acetone in dichloromethane to yield 2.54 g (68%) of 2-(4fluorophenyl)-7-(methylsulfanyl)-pyrazolo[1,5-c]pyrimidine. 1H NMR (CDCl3): δ 8.04 (dd, 2H),7.80 (d, 1H), 7.20 (m, 3H), 6.79 (s, 1H), 2.76 (s, 3H). MS m/z 260 (M+1).

Workup

  1. temperaturere-cooled to 0° C
  2. customdid not exceed 10° C
  3. temperatureto warm to room temperature
  4. temperaturethe mixture heated to 80° C. for 2 hours
  5. temperaturethe mixture heated at 80° C. for 2 hours
  6. temperaturethe mixture heated at 80° C. for 4 hours
  7. temperatureto cool to room temperature
  8. stirringstirred overnight
  9. customThe mixture was partitioned between ethyl acetate and water
  10. extractionThe aqueous phase was extracted with ethyl acetate (2×20 mL)
  11. washThe organic phase was washed with brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified by silica chromatography
  16. washeluting with 1% acetone in dichloromethane

Sources & evidence

ORD record
ord-9d8f012d789d49ed99d5ea5893cb620d
Source dataset
uspto-grants-2007_07
Patent number
US07247626B2

Reaction notes

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