Sodium Cyanide → 7-Tert-butyl-3-[3-chloro-2-(hydroxymethyl)phenyl]-4-oxo-3,4-dihydrophthalazine-5-carbonitrile

HRID 1025558Notes

Reaction equation

HRID 1025558 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13](F)[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=1[CH2:24][OH:25])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[C-:26]#[N:27].[Na+]>CS(C)=O>[C:1]([C:5]1[CH:14]=[C:13]([C:26]#[N:27])[C:12]2[C:11](=[O:16])[N:10]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[CH2:24][OH:25])[N:9]=[CH:8][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 8929Sodium Cyanide2×HCID 594737806-(tert-butyl)-2-(3-chloro-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-one

Product 1

HCID 710082447-Tert-butyl-3-[3-chloro-2-(hydroxymethyl)phenyl]-4-oxo-3,4-dihydrophthalazine-5-carbonitrileYield 57%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a 100 mL round-bottomed flask were added 6-tert-butyl-2-[3-chloro-2-(hydroxymethyl)phenyl]-8-fluorophthalazin-1(2H)-one (671 mg, 1.86 mmol, prepared according to US2010/0222325), sodium cyanide (365 mg, 7.44 mmol) and DMSO (10 mL) to give a light yellow suspension. The mixture was stirred at 80° C. for 16 hrs. Additional sodium cyanide (182 mg, 3.72 mmol) was added and the mixture was further stirred at 80° C. for 60 hrs. The mixture was cooled to room temperature and extracted with ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate and filtered. Solvents were evaporated and the residue was purified through flash column chromatography (220 g silica gel, 0% to 40% acetone in heptane) to give 7-tert-butyl-3-[3-chloro-2-(hydroxymethyl)phenyl]-4-oxo-3,4-dihydrophthalazine-5-carbonitrile as a yellow solid (390 mg, 57% yield).

Workup

  1. customprepared
  2. customto give a light yellow suspension
  3. stirringthe mixture was further stirred at 80° C. for 60 hrs
  4. temperatureThe mixture was cooled to room temperature
  5. extractionextracted with ethyl acetate and water
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customSolvents were evaporated
  10. customthe residue was purified through flash column chromatography (220 g silica gel, 0% to 40% acetone in heptane)

Sources & evidence

ORD record
ord-641c294d5850415c8ac1460c533b79c6
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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