Hydrochloric Acid → HCID 67315090, compound

HRID 1254087Notes

Reaction equation

HRID 1254087 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+].O=[C:23]1[C:31]2[C:26](=[N:27][C:28]([C:32]([OH:34])=[O:33])=[CH:29][CH:30]=2)[CH2:25][O:24]1.Cl>C1COCC1.CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[C:23]1[C:31]2[C:26](=[N:27][C:28]([C:32]([OH:34])=[O:33])=[CH:29][CH:30]=2)[CH2:25][O:24]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 58478830HCID 58478830, compound

Product 1

HCID 67315090HCID 67315090, compoundYield 29.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (177 mg, 1.17 mmol) in THF (2 mL) is treated with a solution of lithium bis(trimethylsilyl)amide (2.9 mL of a 1M solution in THF, 2.3 mmol) dropwise. The resulting solution is stirred at room temperature for 15 min. A solution 5-oxo-5,7-dihydro-furo[3,4-b]pyridine-2-carboxylic acid (105 mg, 0.59 mmol) in dimethylformamide (2 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 3 h and is then poured into a cold 10% aqueous HCl solution (30 mL). The reaction mixture is stirred at room temperature for 65 h. The solid which precipitated from solution is collected by filtration, washed with water and purified by chromatography (silica gel, MeOH/EtOAc). The product containing fractions are concentrated to give the title compound as a reddish solid (54 mg, 29%).

Workup

  1. stirringThe resulting solution is stirred for 3 h
  2. stirringThe reaction mixture is stirred at room temperature for 65 h
  3. customThe solid which precipitated from solution
  4. filtrationis collected by filtration
  5. washwashed with water
  6. custompurified by chromatography (silica gel, MeOH/EtOAc)
  7. additionThe product containing fractions
  8. concentrationare concentrated

Sources & evidence

ORD record
ord-6e741c3e471749b397a0a6ca66f07615
Source dataset
uspto-grants-2013_06
Patent number
US08455535B2

Reaction notes

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