Cyanamide → 2-(4-(N-cyano-S-methylsulfinimidoyl)benzyl)isoindoline-1,3-dione

HRID 527341Notes

Reaction equation

HRID 527341 reaction equation
[CH3:1][S:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])=[CH:5][CH:4]=1.[N:21]#[C:22][NH2:23].CC(C)([O-])C.[K+].BrN1C(=O)CCC1=O>CO>[C:22]([N:23]=[S:2]([C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])=[CH:19][CH:20]=1)[CH3:1])#[N:21]

Participants

6

Reactant 4

HCID 9864CyanamideHCID 67184N-bromobutanimideHCID 79600652-(4-(Methylthio)benzyl)isoindoline-1,3-dioneHCID 23665647Potassium tert-butoxide

Product 1

HCID 867116092-(4-(N-cyano-S-methylsulfinimidoyl)benzyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-(4-(methylthio)benzyl)isoindoline-1,3-dione (preparation 6a, 3.60 g, 12.71 mmol), cyanamide (694 mg, 16.5 mmol) and potassium tert-butoxide (1.71 g, 15.25 mmol) in methanol (30 mL) is treated with N-bromosuccinimide (3.39 g, 19.06 mmol). The mixture is stirred for 1 h and concentrated under reduced pressure. Saturated aqueous Na2S2O3 solution is added and the mixture is extracted twice with dichloromethane. The combined organic layers are dried over Na2SO4 and concentrated under reduced pressure. The residue is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 1:1 to ethyl acetate to ethyl acetate/methanol 4:1). Yield: 2.43 g (59% of theory); ESI mass spectrum: [M+H]+=324; r.t. HPLC: 0.52 min (X001_004).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionSaturated aqueous Na2S2O3 solution is added
  3. extractionthe mixture is extracted twice with dichloromethane
  4. dry with materialThe combined organic layers are dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 1:1 to ethyl acetate to ethyl acetate/methanol 4:1)
  7. customr.t
  8. custom0.52 min (X001_004)

Sources & evidence

ORD record
ord-dac42fcae1fa4b7ea80bf83d3d070d72
Source dataset
uspto-grants-2016_05
Patent number
US09346794B1

Reaction notes

Loading…