N-methyl-2-pyrrolidone → HCID 71272391, compound

HRID 475255Notes

Reaction equation

HRID 475255 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1.[CH3:17][N:18]1C(=O)CCC1>[C-]#N.[C-]#N.[Zn+2]>[O:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH:11]1[N:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[C:2]([C:17]#[N:18])[C:3]=2[CH:4]=[N:5]1

Participants

4

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 574747294-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Product 1

HCID 71272391HCID 71272391, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
85 °C

Procedure

To a mixture of 196 (0.57 g, 2.05 mmol), Zn(CN)2 (264 mg, 2.25 mmol) in NMP (6 mL) under an argon atmosphere was added (Ph3P)4Pd(0) (356 mg, 0.31 mmol). The mixture was heated at 85° C. overnight, cooled, and partitioned between EtOAc (300 mL) and H2O (50 mL). The organic layer was separated and washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with 1% MeOH/DCM to afford 430 mg (75%) of 1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbonitrile (198) as yellow solid: MS (ESI) m/z=228 [M+1]+.

Workup

  1. temperaturecooled
  2. custompartitioned between EtOAc (300 mL) and H2O (50 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by SiO2 chromatography
  8. washeluting with 1% MeOH/DCM

Sources & evidence

ORD record
ord-73434ecbd7534df385ada9867b319574
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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