Hydrochloric Acid → 3-(2-Amino-5-cyanophenyl)-2-(2-diethylaminoethyl)isoindolin-1-one

HRID 231864Notes

Reaction equation

HRID 231864 reaction equation
[C:1]([C:3]1[CH:19]=[CH:18][C:6]2[NH:7][C:8](=[O:17])[C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[CH:11](O)[C:5]=2[CH:4]=1)#[N:2].S(Cl)(Cl)=O.[CH2:24]([N:26]([CH2:30][CH3:31])[CH2:27][CH2:28]N)[CH3:25].Cl.[OH-].[Na+].[N:35]1C=CC=CC=1>C(Cl)Cl.O>[NH2:35][C:6]1[CH:18]=[CH:19][C:3]([C:1]#[N:2])=[CH:4][C:5]=1[CH:11]1[C:10]2[C:9](=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8](=[O:17])[N:7]1[CH2:25][CH2:24][N:26]([CH2:30][CH3:31])[CH2:27][CH3:28]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 60993N,N-DiethylethylenediamineHCID 145020572-cyano-11-hydroxy-5, 11-dihydro-6H-dibenz[b,e]azepin-6-one

Product 1

HCID 30880493-(2-Amino-5-cyanophenyl)-2-(2-diethylaminoethyl)isoindolin-1-oneYield 40.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent4×

Procedure

To a solution of 2.50 g of 2-cyano-11-hydroxy-5, 11-dihydro-6H-dibenz[b,e]azepin-6-one and 1.78 g of pyridine in 40 ml of methylene chloride was added 1.78 g of thionyl chloride under ice cooling. The mixture was stirred for an hour and ice cooling and then at room temperature for 30 minutes. The reaction solution was added to a solution of 5.81 g of N,N-diethylethylenediamine in 50 ml of methylene chloride at -5° to 0° C. with stirring. After stirring for an hour under ice cooling, 5 ml of water was added thereto. Further 200 ml of methylene chloride and 100 ml of water were added to the reaction mixture, and pH was adjusted to 1 with 4N-hydrochloric acid. After shaking, the organic layer was discarded and 200 ml of methylene chloride was added to the aqueous layer. The pH was adjusted to 10 with 10N-sodium hydroxide solution. After shaking, the aqueous layer was discarded and the organic layer was washed with saturated aqueous sodium chloride solution. After drying over anhydrous sodium sulfate, the organic layer was concentrated under reduced pressure. The crude product obtained was subjected to silica gel column chromatography (eluting solvent, ethyl acetate:hexane:triethylamine=16:4:1). A major fraction was concentrated to dryness under reduced pressure to give 1.42 g of 3-(2-amino-5-cyanophenyl)-2-(2-diethylaminoethyl)isoindolin-1-one (Compound 31).

Workup

  1. stirringwith stirring
  2. stirringAfter stirring for an hour under ice cooling
  3. stirringAfter shaking
  4. stirringAfter shaking
  5. washthe organic layer was washed with saturated aqueous sodium chloride solution
  6. dry with materialAfter drying over anhydrous sodium sulfate
  7. concentrationthe organic layer was concentrated under reduced pressure
  8. customThe crude product obtained
  9. washwas subjected to silica gel column chromatography (eluting solvent, ethyl acetate:hexane:triethylamine=16:4:1)
  10. concentrationA major fraction was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-0c805bc1ddf64c60a4bcb73e66abb450
Source dataset
uspto-grants-1989_07
Patent number
US04849441

Reaction notes

Loading…