Imidazole → HCID 131734154, compound

HRID 717069Notes

Reaction equation

HRID 717069 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][N:11]=2)[CH2:6][CH2:5]1.N1C=CN=C1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>CN(C=O)C.CCOC(C)=O>[C:26]([Si:23]([CH3:25])([CH3:24])[O:1][CH2:2][CH2:3][N:4]1[CH2:5][CH2:6][N:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][N:11]=2)[CH2:8][CH2:9]1)([CH3:29])([CH3:28])[CH3:27]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 25918955HCID 25918955, compound

Product 1

HCID 131734154HCID 131734154, compoundYield 75.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-nicotinonitrile (350 mg, 1.51 mmol) and imidazole (236 mg, 3.47 mmol) in anhydrous DMF (3 mL) was added TBDMS chloride (295 mg, 1.96 mmol) in anhydrous DMF (2 mL) and the reaction mixture stirred for 16 h at RT. The reaction mixture was diluted with EtOAc (5 mL) and washed with water (10 mL) and brine (10 mL). The organic phase was separated, passed through a phase separation cartridge and concentrated in vacuo. The crude residue was purified on silica gel column chromatography eluting with 30% EtOAc/isohexane, and increasing the polarity to 50% EtOAc/isohexane to afford 6-{4-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-piperazin-1-yl}-nicotinonitrile as a pale yellow solid (394 mg, 75%).

Workup

  1. washwashed with water (10 mL) and brine (10 mL)
  2. customThe organic phase was separated
  3. custompassed through a phase separation cartridge
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified on silica gel column chromatography
  6. washeluting with 30% EtOAc/isohexane
  7. temperatureincreasing the polarity to 50% EtOAc/isohexane

Sources & evidence

ORD record
ord-32ce206b899a455197b7a5eeaac59ea7
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

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