Acetonitrile → HCID 69448731, compound

HRID 1296702Notes

Reaction equation

HRID 1296702 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[C:15]3[N:10]([C:11]([S:17][CH3:18])=[N:12][CH:13]=[CH:14]3)[N:9]=2)=[CH:4][CH:3]=1.[C:19](OC(=O)C)(=[O:21])[CH3:20].B(F)(F)F.CCOCC.C(#N)C>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:16]([C:19](=[O:21])[CH3:20])=[C:15]3[N:10]([C:11]([S:17][CH3:18])=[N:12][CH:13]=[CH:14]3)[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 7918Acetic Anhydride2×HCID 8000Boron trifluoride etherate2×HCID 17956316HCID 17956316, compound

Product 1

HCID 69448731HCID 69448731, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

To a solution of 2-(4-fluorophenyl)-7-(methylsulfanyl)pyrazolo[1,5-c]pyrimidine (150 mg, 0.58 mmol) in toluene (10 mL) was added acetic anhydride (0.065 mL, 0.69 mmol), followed by boron trifluoride diethyl etherate (0.080 ml, 0.64 mmol). An additional 10 mL of toluene was added and the mixture heated to 90° C. Acetonitrile (10 mL) was added to the reaction and the mixture heated at 70° C. for additional 16 hours. Additional acetic anhydride (0.11 mL, 1.1 mmol) and boron trifluoride diethyl etherate (0.15 ml, 1.2 mmol) were added dropwise to the reaction mixture at 90° C. The reaction was stirred for 1 hour, cooled to room temperature, stirred for 16 hours, and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The ethyl acetate layer was washed with brine, dried over magnesium sulfate, filtered, concentrated, and the residue purified by silica gel chromatography eluting with 10% ethyl acetate in hexanes to yield 110 mg (63%) of 1-[2-(4-fluorophenyl)-7-(methylsulfanyl)pyrazolo[1,5-c]pyrimidin-3-yl]ethanone. 1H NMR (CDCl3): δ 8.13 (d, 1H), 7.98 (d, 1H), 7.65 (dd, 2H), 7.27 (m, 2H), 2.77 (s, 3H), 2.23 (s, 3H). MS m/z 302 (M+1).

Workup

  1. temperaturethe mixture heated at 70° C. for additional 16 hours
  2. temperaturecooled to room temperature
  3. stirringstirred for 16 hours
  4. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  5. washThe ethyl acetate layer was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe residue purified by silica gel chromatography
  10. washeluting with 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-a2611ca33b734352b9d8f1a4eeb1fb9d
Source dataset
uspto-grants-2007_07
Patent number
US07247626B2

Reaction notes

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