Sodium hydride → methyl 4-(acetylamino)-13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylate

HRID 1518231Notes

Reaction equation

HRID 1518231 reaction equation
[H-].[Na+].[C:3]([NH:6][C:7]1[C:8]([NH:32][C:33](=[O:36])[CH2:34]Cl)=[C:9]([C:13]2[NH:14][C:15]3[C:20]([C:21]=2[CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:19][CH:18]=[C:17]([C:28]([O:30][CH3:31])=[O:29])[CH:16]=3)[CH:10]=[CH:11][CH:12]=1)(=[O:5])[CH3:4]>CN(C=O)C>[C:3]([NH:6][C:7]1[C:8]2[NH:32][C:33](=[O:36])[CH2:34][N:14]3[C:15]4[CH:16]=[C:17]([C:28]([O:30][CH3:31])=[O:29])[CH:18]=[CH:19][C:20]=4[C:21]([CH:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[C:13]3[C:9]=2[CH:10]=[CH:11][CH:12]=1)(=[O:5])[CH3:4]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 68706281methyl 2-{3-(acetylamino)-2-[(chloroacetyl)amino]phenyl}-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 68705017methyl 4-(acetylamino)-13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylateYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (60% dispersion in mineral oil) (1.7 eq) was added to a stirred solution of methyl 2-{3-(acetylamino)-2-[(chloroacetyl)amino]phenyl}-3-cyclohexyl-1H-indole-6-carboxylate in anhydrous DMF (0.02 M) at RT under N2. The reaction was stirred vigorously for 1 h before quenching with 1N HCl (aq) and extracting into EtOAc. The aqueous phase was extracted a second time with EtOAc and the combined organics washed well with 1N HCl (aq), water and brine before being dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford the title compound as a brown glass (94%). The material was taken on in the subsequent step without further purification. MS (ES+) m/z 446 (M+H)+.

Workup

  1. custombefore quenching with 1N HCl (aq)
  2. extractionextracting into EtOAc
  3. extractionThe aqueous phase was extracted a second time with EtOAc
  4. washthe combined organics washed well with 1N HCl (aq), water and brine
  5. dry with materialbefore being dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8d20f151ffbc443fbd38540eb27c5df8
Source dataset
uspto-grants-2012_07
Patent number
US08232390B2

Reaction notes

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