Dicyclohexylcarbodiimide → 5-[(2-dimethylaminoacetyloxy)methyl]-7-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride

HRID 5587

Reaction equation

HRID 5587 reaction equation
CN(C1C=CC=CN=1)C.Cl.CN(C1C=CC=CN=1)C.Cl.[CH3:21][N:22]([CH3:27])[CH2:23][C:24]([OH:26])=[O:25].C1(N=C=NC2CCCCC2)CCCCC1.C(=O)([O-])O.[Na+].O[CH2:49][CH:50]1[C:56]2[CH:57]=[C:58]([Cl:61])[CH:59]=[CH:60][C:55]=2[N:54]([C:62](=[O:79])[C:63]2[CH:68]=[CH:67][C:66]([NH:69][C:70](=[O:78])[C:71]3[CH:76]=[CH:75][CH:74]=[CH:73][C:72]=3[CH3:77])=[CH:65][CH:64]=2)[CH2:53][CH2:52][CH2:51]1>C(Cl)(Cl)Cl.C(O)(=O)C.CO>[ClH:61].[CH3:21][N:22]([CH3:27])[CH2:23][C:24]([O:26][CH2:49][CH:50]1[C:56]2[CH:57]=[C:58]([Cl:61])[CH:59]=[CH:60][C:55]=2[N:54]([C:62](=[O:79])[C:63]2[CH:68]=[CH:67][C:66]([NH:69][C:70](=[O:78])[C:71]3[CH:76]=[CH:75][CH:74]=[CH:73][C:72]=3[CH3:77])=[CH:65][CH:64]=2)[CH2:53][CH2:52][CH2:51]1)=[O:25]

Participants

10

Reactant 6

HCID 10868DicyclohexylcarbodiimideHCID 218852-DimethylaminopyridineHCID 75605N,N-Dimethylglycine hydrochlorideHCID 516892Sodium BicarbonateHCID 189174195-hydroxymethyl-7-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepineHCID 22461520Dimethylaminopyridine hydrochloride

Product 1

HCID 189173225-[(2-dimethylaminoacetyloxy)methyl]-7-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochlorideYield 141.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

In a solution of 5-hydroxymethyl-7-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.4 g) in chloroform (10 ml) are dissolved with heating dimethylaminopyridine (0.41 g) and dimethylaminopyridine hydrochloride (0.35 g), and thereto is added N,N-dimethylglycine hydrochloride (0.15 g) at room temperature with stirring, and further added dicyclohexylcarbodiimide (0.46 g). The mixture is stirred at room temperature overnight. To the mixture are added methanol (1.3 ml) and acetic acid (0.4 ml), and the mixture is stirred at room temperature for two hours. Saturated aqueous sodium hydrogen carbonate solution is added to the reaction solution, and the mixture is extracted with dichloromethane, and the extract is dried over magnesium sulfate. The solvent is distilled off under reduced pressure, and the resulting residue is purified by silica gel column chromatography (eluent; methyl acetate), and thereto is added a mixture of hydrochloric acid/methanol. The mixture is stirred at room temperature for one hour to give 5-[(2-dimethylaminoacetyloxy)methyl]-7-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (0.36 g) as colorless amorphous.

Workup

  1. stirringThe mixture is stirred at room temperature overnight
  2. stirringthe mixture is stirred at room temperature for two hours
  3. extractionthe mixture is extracted with dichloromethane
  4. dry with materialthe extract is dried over magnesium sulfate
  5. distillationThe solvent is distilled off under reduced pressure
  6. customthe resulting residue is purified by silica gel column chromatography (eluent; methyl acetate)
  7. additionis added
  8. additiona mixture of hydrochloric acid/methanol
  9. stirringThe mixture is stirred at room temperature for one hour

Sources & evidence

ORD record
ord-95de830301e84a0d9f33eedda961e5bd
Source dataset
uspto-grants-1993_09
Patent number
US05244898

Linked notes

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