Dicyclohexylcarbodiimide → (3RS)-1,3-dihydro-3-(2-indolylcarbonylamino)-5-phenyl-1-{2-((RS)-2-tetrahydropyranyloxy)ethyl}-2H-1,4-benzodiazepine-2-one

HRID 1769856Notes

Reaction equation

HRID 1769856 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.[C:38]1([C:44]2[C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][C:49]=3[N:48]([CH2:55][CH2:56][O:57][CH:58]3[CH2:63][CH2:62][CH2:61][CH2:60][O:59]3)[C:47](=[O:64])[CH:46]([NH2:65])[N:45]=2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(Cl)(Cl)Cl>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([NH:65][CH:46]1[N:45]=[C:44]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:50]2[CH:51]=[CH:52][CH:53]=[CH:54][C:49]=2[N:48]([CH2:55][CH2:56][O:57][CH:58]2[CH2:63][CH2:62][CH2:61][CH2:60][O:59]2)[C:47]1=[O:64])=[O:12]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 72899Indole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 14800304(3RS)-1,3-dihydro-5-phenyl-3-amino-1-{2-((RS)-2-tetrahydropyranyloxy) ethyl}-2H-1,4-benzodiazepine-2-one2×

Product 1

HCID 14800305(3RS)-1,3-dihydro-3-(2-indolylcarbonylamino)-5-phenyl-1-{2-((RS)-2-tetrahydropyranyloxy)ethyl}-2H-1,4-benzodiazepine-2-oneYield 76%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of indole-2-carboxylic acid (0.19 g), N-hydroxybenzotriazole (0.16 g) and N,N'-dicyclohexylcarbodiimide (0.24 g) in chloroform (10 ml) was added a mixture (0.43 g) of (3RS)-1,3-dihydro-5-phenyl-3-amino-1-{2-((RS)-2-tetrahydropyranyloxy) ethyl }-2H-1,4-benzodiazepine-2-one and (3RS)-1,3-dihydro-5-phenyl-3-amino-1-{2-((SR)-2-tetrahydropyranyloxy) ethyl }-2H-1,4-benzodiazepine-2-one at ambient temperature under stirring. The mixture was stirred for 2 hours under the same conditions. The resultant precipitate was filtered off. The combined filtrate and washings were evaporated under reduced pressure and the residual oil (1.20 g) was subjected to column chromatography on silica gel with an eluent of a mixture of chloroform and ethyl acetate (10:1) to give a mixture (white powder, 0.45 g) of (3RS)-1,3-dihydro-3-(2-indolylcarbonylamino)-5-phenyl-1-{2-((RS)-2-tetrahydropyranyloxy)ethyl}-2H-1,4-benzodiazepine-2-one and (3RS)-1,3-dihydro-3-(2 -indolylcarbonylamino )-5-phenyl-1-{2-((SR)-2-tetrahydropyranyloxy) ethyl}-2H-1,4-benzodiazepine-2-one.

Workup

  1. stirringThe mixture was stirred for 2 hours under the same conditions
  2. filtrationThe resultant precipitate was filtered off
  3. customThe combined filtrate and washings were evaporated under reduced pressure
  4. additionthe residual oil (1.20 g) was subjected to column chromatography on silica gel with an eluent of a mixture of chloroform and ethyl acetate (10:1)

Sources & evidence

ORD record
ord-cfde013eeeef419da65d674dcefdf562
Source dataset
uspto-grants-1995_01
Patent number
US05382664

Reaction notes

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