HCID 67147254, compound → HCID 11992238, compound

HRID 251486Notes

Reaction equation

HRID 251486 reaction equation
[C:1]([N:4]1[CH2:26][C:12]2([CH2:17][CH2:16][N:15]([C:18]3([C:24]#N)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5]1)(=[O:3])[CH3:2].C[Mg]Br>O1CCCC1>[CH3:24][C:18]1([N:15]2[CH2:14][CH2:13][C:12]3([C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:26]3)[CH2:17][CH2:16]2)[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

4

Reactant 2

HCID 67147254HCID 67147254, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 11992238HCID 11992238, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The crude 1-(2-acetyl-2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)cyclohexanecarbonitrile 8a was dissolved in anhydrous tetrahydrofuran (1.0 mL) and treated with methylmagnesium bromide (1.0 mL 1.0 M solution in butyl ether, 1.0 mmol). The vial was flushed with nitrogen and stirred at room temperature for 3 hours. The reaction was diluted with ethyl acetate (5.0 mL), quenched with saturated aqueous ammonium chloride (1.0 mL) and stirred overnight at room temperature. The layers were separated, the organic layer concentrated under reduced pressure and purified by reverse-phase HPLC (1-25% CH3CN—H2O gradient, with 0.05% TFA, 15 min) to provide 1-(1′-(1-methylcyclohexyl) -1H-spiro[isoquinoline-4,4′-piperidine]-2(3H)-yl)ethanone. LC/MS m/z [M+H]+ 341.2 retention time 1.83 min (10-99% CH3CN—H2O gradient, with 0.05% TFA, 5 min).

Workup

  1. customThe vial was flushed with nitrogen
  2. additionThe reaction was diluted with ethyl acetate (5.0 mL)
  3. customquenched with saturated aqueous ammonium chloride (1.0 mL)
  4. stirringstirred overnight at room temperature
  5. customThe layers were separated
  6. concentrationthe organic layer concentrated under reduced pressure
  7. custompurified by reverse-phase HPLC (1-25% CH3CN—H2O gradient, with 0.05% TFA, 15 min)

Sources & evidence

ORD record
ord-50ae882e19af4ef795fd799df2abf0ed
Source dataset
uspto-grants-2011_01
Patent number
US07863449B2

Reaction notes

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