Piperidine → HCID 178487036, compound

HRID 447548Notes

Reaction equation

HRID 447548 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[C:7](=[O:13])[CH2:6]2.[I:14][C:15]1[C:23]2[C:18](=[CH:19][C:20]([CH:24]=O)=[CH:21][CH:22]=2)[NH:17][N:16]=1.N1CCCC[CH2:27]1.[H-].[Na+].[I-].C[S+](C)(C)=O>CN(C=O)C.CO>[I:14][C:15]1[C:23]2[C:18](=[CH:19][C:20]([C@H:24]3[C@@:6]4([C:5]5[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=5)[N:8]([CH3:12])[C:7]4=[O:13])[CH2:27]3)=[CH:21][CH:22]=2)[NH:17][N:16]=1

Participants

8

Reactant 5

HCID 8082PiperidineHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 91021941,3-Dihydro-5-methoxy-1-methyl-2H-indol-2-oneHCID 178519327HCID 178519327, compound

Product 1

HCID 178487036HCID 178487036, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A vial was charged with 5-methoxy-1-methylindolin-2-one (144 mg, 0.813 mg), 3-iodo-1H-indazole-6-carbaldehyde (221 mg, 0.813 mmol), MeOH (4.0 mL), and piperidine (7 uL, 0.081 mmol). The mixture was reacted at 50° C. for 18 h. The resulting orange precipitate was filtered, washed with MeOH and then dried under high vacuum. The orange solid was then added to a suspension of NaH (60% wt.) (155 mg, 3.87 mmol), trimethylsulfoxonium iodide (284 mg, 1.29 mmol), and DMF (3.0 mL) that had been pre-stirred at room temperature for 30 minutes. This mixture was heated to 40° C. for 2 h. The reaction was cooled to 0° C., quenched with NH4Cl (sat.) (2 mL) and extracted with EtOAc (100 mL). The organic layer was separated, washed with brine (10 mL) and dried over MgSO4. The solvent was removed and the residue purified by column chromatography (silica gel, Hexanes/Acetone, 5:1 to 3:1) to give the title compound as a pink solid give (205 mg, 57%); MS ESI 446.0 [M+H]+, calcd for [C19H16N3O2+H]+ 446.04.

Workup

  1. customThe mixture was reacted at 50° C. for 18 h
  2. filtrationThe resulting orange precipitate was filtered
  3. washwashed with MeOH
  4. customdried under high vacuum
  5. temperatureThis mixture was heated to 40° C. for 2 h
  6. temperatureThe reaction was cooled to 0° C.
  7. customquenched with NH4Cl (sat.) (2 mL)
  8. extractionextracted with EtOAc (100 mL)
  9. customThe organic layer was separated
  10. washwashed with brine (10 mL)
  11. dry with materialdried over MgSO4
  12. customThe solvent was removed
  13. customthe residue purified by column chromatography (silica gel, Hexanes/Acetone, 5:1 to 3:1)

Sources & evidence

ORD record
ord-bd2e1f6f2e734e93980a71d9aa3859df
Source dataset
uspto-grants-2013_07
Patent number
US08481525B2

Reaction notes

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