Hydrochloric Acid → HCID 67315882, compound

HRID 1011382Notes

Reaction equation

HRID 1011382 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]([CH2:40][CH3:41])[CH2:25][CH2:26][NH:27][C:28]([C:30]1[N:35]=[C:34]2[CH2:36][O:37][C:38](=O)[C:33]2=[CH:32][CH:31]=1)=[O:29])[CH3:23].Cl>C1COCC1.O1CCOCC1>[CH2:40]([N:24]([CH2:22][CH3:23])[CH2:25][CH2:26][NH:27][C:28]([C:30]1[N:35]=[C:34]2[CH2:36][O:37][C:38](=[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:33]2=[CH:32][CH:31]=1)=[O:29])[CH3:41]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 67314895HCID 67314895, compound

Product 1

HCID 67315882HCID 67315882, compoundYield 49.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (76 mg, 0.46 mmol) in THF (3 mL) is treated with a solution of lithium bis(trimethylsilyl)amide (1.2 mL of a 1 M solution in THF, 1.2 mmol) dropwise. The resulting solution is stirred at room temperature for 10 min. A solution of 5-oxo-5,7-dihydro-furo[3,4-b]pyridine-2-carboxylic acid (2-diethylamino-ethyl)-amide (70 mg, 0.25 mmol) in THF (2 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 4 h and is poured into a cold 4M HCl solution in dioxane (3 mL) at 0° C. The resulting mixture is stirred at room temperature overnight. The reaction mixture is concentrated to partially remove the dioxane and is then partitioned between EtOAc and saturated aqueous NaHCO3 solution. The organic phase is collected and the aqueous phase is extracted with additional EtOAc. The combined organic extracts are dried (Na2SO4), filtered and concentrated. The residue is purified by chromatography (silica gel, MeOH-Chloroform). The product containing fraction are concentrated and the residue is treated with EtOAc-hexane (1:1). The solid is collected by filtration to give the title compound as an orange solid (51 mg, 49%).

Workup

  1. stirringThe resulting solution is stirred for 4 h
  2. stirringThe resulting mixture is stirred at room temperature overnight
  3. concentrationThe reaction mixture is concentrated
  4. customto partially remove the dioxane
  5. customis then partitioned between EtOAc and saturated aqueous NaHCO3 solution
  6. customThe organic phase is collected
  7. extractionthe aqueous phase is extracted with additional EtOAc
  8. dry with materialThe combined organic extracts are dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue is purified by chromatography (silica gel, MeOH-Chloroform)
  12. additionThe product containing fraction
  13. concentrationare concentrated
  14. additionthe residue is treated with EtOAc-hexane (1:1)
  15. filtrationThe solid is collected by filtration

Sources & evidence

ORD record
ord-71e9a3c0df654ade8e0dcb4a49bc75ba
Source dataset
uspto-grants-2011_07
Patent number
US07977351B2

Reaction notes

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