Hydrochloric Acid → HCID 67315022, compound

HRID 1254101Notes

Reaction equation

HRID 1254101 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+].[CH:22]([C:24]1[N:29]=[C:28]2[CH2:30][O:31][C:32](=O)[C:27]2=[CH:26][CH:25]=1)=C.Cl>C1COCC1>[CH2:6]([N:7]([CH2:22][C:24]1[N:29]=[C:28]2[CH2:30][O:31][C:32](=[C:5]3[C:4]4[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=4)[NH:7][C:6]3=[O:11])[C:27]2=[CH:26][CH:25]=1)[CH2:8][CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 58478753HCID 58478753, compound

Product 1

HCID 67315022HCID 67315022, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (3.38 g, 22.4 mmol.) in THF (100 mL) is treated with a solution of lithium bis(trimethylsilyl)amide (45 mL of a 1 M solution in THF, 45 mmol) dropwise. The resulting solution is stirred at room temperature for 15 min and then treated with 2-vinyl-7H-furo[3,4-b]pyridin-5-one (1.2 g, 7.45 mmol) in one portion. The reaction mixture is stirred at room temperature for 2 h. The reaction mixture is poured into a cold aqueous 2 N HCl solution (200 mL). The ice bath is removed and the reaction mixture is heated at 50° C. for 2 h and then stirred at room temperature overnight. The reaction mixture is treated with 100 mL ice water and stirred for 30 min. The yellow solid is collected by filtration and dried. The solid is purified by chromatography (silica gel, MeOH-Chloroform) and the product containing fractions concentrated. The residue is triturated with MeOH and the solid is collected by filtration and dried to give 5-Fluoro-3-(2-vinyl-7H-furo[3,4-b]pyridin-5-ylidene)-1,3-dihydro-indol-2-one (Example 6) as an orange solid (0.82 g, 37%). The filtrate is absorbed to silica gel and subjected to chromatography (silica gel, EtOAc-hexane) to afford (Example 28) as a yellow solid (50 mg, 1.5%).

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 2 h
  2. customThe ice bath is removed
  3. temperaturethe reaction mixture is heated at 50° C. for 2 h
  4. stirringstirred at room temperature overnight
  5. additionThe reaction mixture is treated with 100 mL ice water
  6. stirringstirred for 30 min
  7. filtrationThe yellow solid is collected by filtration
  8. customdried
  9. customThe solid is purified by chromatography (silica gel, MeOH-Chloroform)
  10. additionthe product containing fractions
  11. concentrationconcentrated
  12. customThe residue is triturated with MeOH
  13. filtrationthe solid is collected by filtration
  14. customdried

Sources & evidence

ORD record
ord-2aafd786f8af47c59ec0b08a2aa1c8cd
Source dataset
uspto-grants-2013_06
Patent number
US08455535B2

Reaction notes

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