Water → 9-Chloro-7-[2-(2,4-di-t-amylphenoxy)butanoylamino]-6-hydroxy-1,5-benzodiazepin-2,4-dione

HRID 1253015Notes

Reaction equation

HRID 1253015 reaction equation
[NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([Cl:9])[CH:5]=[C:4]([NH:10][C:11](=[O:32])[CH:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([CH2:25][CH3:26])([CH3:24])[CH3:23])=[CH:18][C:17]=2[C:27]([CH2:30][CH3:31])([CH3:29])[CH3:28])[CH2:13][CH3:14])[C:3]=1[OH:33].[C:34](Cl)(=[O:39])[CH2:35][C:36](Cl)=[O:37].O.C(OCC)(=O)C>C1C=CC=CC=1>[Cl:9][C:6]1[C:7]2=[N:8][C:34](=[O:39])[CH2:35][C:36](=[O:37])[N:1]=[C:2]2[C:3]([OH:33])=[C:4]([NH:10][C:11](=[O:32])[CH:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([CH2:25][CH3:26])([CH3:24])[CH3:23])=[CH:18][C:17]=2[C:27]([CH2:30][CH3:31])([CH3:29])[CH3:28])[CH2:13][CH3:14])[CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 74269Propanedioyl dichlorideHCID 201378102,3-Diamino-4-chloro-6-[2-(2,4-di-t-amylphenoxy)butanoylamino]phenol

Product 1

HCID 1355831249-Chloro-7-[2-(2,4-di-t-amylphenoxy)butanoylamino]-6-hydroxy-1,5-benzodiazepin-2,4-dione

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

In 250 ml of benzene was dissolved 17 g of the resulting 2,3-diamino-4-chloro-6-[2-(2,4-di-t-amylphenoxy)butanoylamino]phenol, and a solution of 5.8 g of malonyl dichloride in 100 ml of benzene was slowly added to the solution at room temperature while stirring. After the dropwise addition, the reaction mixture was stirred for 1 hour. Water and ethyl acetate were added to the reaction mixture to effect extraction. The extract was concentrated, and the residue was purified by silica gel column chromatography (chloroform/ethyl acetate=2/1 by volume) to obtain 4.2 g of the desired coupler (Coupler 3) having a melting point of 193° to 195° C.

Workup

  1. additionAfter the dropwise addition
  2. stirringthe reaction mixture was stirred for 1 hour
  3. concentrationThe extract was concentrated
  4. customthe residue was purified by silica gel column chromatography (chloroform/ethyl acetate=2/1 by volume)
  5. customto obtain 4.2 g of the desired coupler (Coupler 3)

Sources & evidence

ORD record
ord-e9d82619dfb94e45b07ae419dd37f220
Source dataset
uspto-grants-1988_05
Patent number
US04746602

Reaction notes

Loading…