Hydrochloric Acid → HCID 67315650, compound

HRID 1254091Notes

Reaction equation

HRID 1254091 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+].[OH:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]2[N:40]=[C:39]3[CH2:41][O:42][C:43](=O)[C:38]3=[CH:37][CH:36]=2)[CH2:30][CH2:29]1.Cl>C1COCC1>[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:43]1[C:38]2[C:39](=[N:40][C:35]([CH2:34][N:31]3[CH2:32][CH2:33][N:28]([CH2:27][CH2:26][O:25][CH2:24][CH2:23][OH:22])[CH2:29][CH2:30]3)=[CH:36][CH:37]=2)[CH2:41][O:42]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 58478847HCID 58478847, compound

Product 1

HCID 67315650HCID 67315650, compoundYield 20.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-fluoro-1,3-dihydro-indol-2-one (72 mg, 0.47 mmol) in THF (2 mL) is treated with a solution of lithium bis(trimethylsilyl)amide (1.2 mL of a 1M solution in THF, 1.2 mmol) dropwise. The resulting solution is stirred for 10 min at room temperature. A solution 2-{4-[2-(2-hydroxy-ethoxy)-ethyl]-piperazin-1-ylmethyl}-7H-furo[3,4-b]pyridin-5-one (77 mg, 0.24 mmol) in THF (1.5 mL) and added dropwise to the reaction mixture. The resulting solution is stirred for 4 h and is then treated with HCl (4M in dioxane, 5 mL) at 0° C. The reaction mixture is stirred at room temperature for 48 h. The reaction mixture is concentrated and the residue is treated with saturated aqueous NaHCO3. The aqueous solution is extracted with EtOAc (2×). The combined organic extracts are dried (MgSO4) and concentrated. The residue is purified by chromatography (silica gel, gradient elution 20:1 chloroform:MeOH to 10:1 chloroform:MeOH). The product containing fractions are concentrated and the residue is triturated from EtOAc-hexane and collected by filtration to give the title compound as a yellow solid (22 mg, 20%).

Workup

  1. stirringThe resulting solution is stirred for 4 h
  2. stirringThe reaction mixture is stirred at room temperature for 48 h
  3. concentrationThe reaction mixture is concentrated
  4. additionthe residue is treated with saturated aqueous NaHCO3
  5. extractionThe aqueous solution is extracted with EtOAc (2×)
  6. dry with materialThe combined organic extracts are dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue is purified by chromatography (silica gel, gradient elution 20:1 chloroform:MeOH to 10:1 chloroform:MeOH)
  9. additionThe product containing fractions
  10. concentrationare concentrated
  11. customthe residue is triturated from EtOAc-hexane
  12. filtrationcollected by filtration

Sources & evidence

ORD record
ord-af4105d778aa4c8f8a6891cc5566a8e1
Source dataset
uspto-grants-2013_06
Patent number
US08455535B2

Reaction notes

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