Hydrochloric Acid → HCID 67315663, compound

HRID 1011404Notes

Reaction equation

HRID 1011404 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:22]([CH:24]1[C:32]2[CH:31]=[C:30]([C:33]([F:36])([F:35])[F:34])[N:29]=[CH:28][C:27]=2[C:26](=O)[O:25]1)[CH3:23].Cl>C1COCC1>[CH2:22]([CH:24]1[C:32]2[CH:31]=[C:30]([C:33]([F:36])([F:35])[F:34])[N:29]=[CH:28][C:27]=2[C:26](=[C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=3)[NH:7][C:6]2=[O:11])[O:25]1)[CH3:23]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 67315490HCID 67315490, compound

Product 1

HCID 67315663HCID 67315663, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (99 mg, 0.66 mmol.) in THF (2 mL) is cooled to 0° C. under an Argon atmosphere and treated with a solution of lithium bis(trimethylsilyl)amide (1.3 mL of a 1 M solution in THF, 1.3 mmol) dropwise. The resulting solution is stirred at 0° C. for 10 min and warmed to room temperature. A solution of 1-ethyl-6-trifluoromethyl-1H-furo[3,4-c]pyridin-3-one, (100 mg, 0.44 mmol) in THF (2 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 4 h. The reaction mixture is poured into aqueous 10% HCl solution (50 mL). The resulting mixture is heated to 90° C. for 45 min and then stirred at room temperature for 36 h. The precipitate which formed is collected by filtration and dried. The solid obtained is purified by chromatography (silica gel, 40% EtOAc/hexane). The product containing fractions are concentrated to give the title compound as a yellow solid (30 mg, 19%).

Workup

  1. temperaturewarmed to room temperature
  2. stirringThe resulting solution is stirred for 4 h
  3. temperatureThe resulting mixture is heated to 90° C. for 45 min
  4. stirringstirred at room temperature for 36 h
  5. customThe precipitate which formed
  6. filtrationis collected by filtration
  7. customdried
  8. customThe solid obtained
  9. customis purified by chromatography (silica gel, 40% EtOAc/hexane)
  10. additionThe product containing fractions
  11. concentrationare concentrated

Sources & evidence

ORD record
ord-2ac7df5fd8b342c6a7562a92d20e0a97
Source dataset
uspto-grants-2011_07
Patent number
US07977351B2

Reaction notes

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