Hydrochloric Acid → HCID 67315022, compound

HRID 1011343Notes

Reaction equation

HRID 1011343 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]([N:24]([CH2:27][C:28]1[N:33]=[C:32]2[CH2:34][O:35][C:36](=O)[C:31]2=[CH:30][CH:29]=1)[CH2:25][CH3:26])[CH3:23].Cl>C1COCC1>[CH2:22]([N:24]([CH2:27][C:28]1[N:33]=[C:32]2[CH2:34][O:35][C:36](=[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:31]2=[CH:30][CH:29]=1)[CH2:25][CH3:26])[CH3:23]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 58478769HCID 58478769, compound

Product 1

HCID 67315022HCID 67315022, compoundYield 39.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (88 mg, 0.58 mmol.) in THF (4 mL) is placed under an argon atmosphere cooled in an ice bath. A solution of lithium bis(trimethylsilyl)amide (1.55 mL of a 1M solution in THF, 1.55 mmol) is added slowly at 0° C. and the resulting solution is stirred for 20 min. The ice-bath is then removed and a solution of 2-diethylaminomethyl-7H-furo[3,4-b]pyridin-5-one (85 mg, 0.39 mmol) in THF (1 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 3 h and then poured into 10% aqueous HCl solution (20 mL) and stirred for 48 h at room temperature. The solid which precipitated from solution is collected by filtration. The solid is purified by chromatography (silica gel, gradient elution, 100:1 Chloroform/MeOH to 10:1 Chloroform/MeOH). The product containing fractions are concentrated to give the title compound (54 mg, 39%).

Workup

  1. temperaturecooled in an ice bath
  2. customThe ice-bath is then removed
  3. stirringThe resulting solution is stirred for 3 h
  4. stirringstirred for 48 h at room temperature
  5. customThe solid which precipitated from solution
  6. filtrationis collected by filtration
  7. customThe solid is purified by chromatography (silica gel, gradient elution, 100:1 Chloroform/MeOH to 10:1 Chloroform/MeOH)
  8. additionThe product containing fractions
  9. concentrationare concentrated

Sources & evidence

ORD record
ord-ea75c1b6021147a6b57570ebb791949d
Source dataset
uspto-grants-2011_07
Patent number
US07977351B2

Reaction notes

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