Cesium carbonate → tert-butyl N-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-1-[4-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-3-(tert-butoxycarbonylamino)-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-3-yl]carbamate

HRID 1481938Notes

Reaction equation

HRID 1481938 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:15](=[O:16])[NH:14][C:13]2[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=2[N:11]([C:21]([C:23]2[CH:50]=[CH:49][C:26]([C:27]([N:29]3[C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=4[NH:33][C:32](=[O:40])[C@@H:31]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:30]3)=[O:28])=[CH:25][CH:24]=2)=[O:22])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:51][C:52]1[CH:53]=[C:54]2[C:59](=[CH:60][CH:61]=1)[C:58]([CH2:62]Cl)=[C:57]([O:64][CH3:65])[CH:56]=[CH:55]2.[C:66](=[O:69])([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[Br:51][C:52]1[CH:53]=[C:54]2[C:59](=[CH:60][CH:61]=1)[C:58]([CH2:62][N:33]1[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[N:29]([C:27](=[O:28])[C:26]3[CH:25]=[CH:24][C:23]([C:21]([N:11]4[C:12]5[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=5[N:14]([CH2:62][C:58]5[C:59]6[C:54](=[CH:53][C:52]([Br:51])=[CH:61][CH:60]=6)[CH:55]=[CH:56][C:57]=5[O:69][CH3:66])[C:15](=[O:16])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:10]4)=[O:22])=[CH:50][CH:49]=3)[CH2:30][C@H:31]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[C:32]1=[O:40])=[C:57]([O:64][CH3:65])[CH:56]=[CH:55]2

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 7371226-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 90220967tert-butyl N-[(3S)-5-[4-[(3S)-3-(tert-butoxycarbonylamino)-2-oxo-3,4-dihydro-1H-1,5-benzodiazepine-5-carbonyl]benzoyl]-2-oxo-3,4-dihydro-1H-1,5-benzodiazepin-3-yl]carbamate

Product 1

HCID 90220903tert-butyl N-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-1-[4-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-3-(tert-butoxycarbonylamino)-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-3-yl]carbamateYield 65%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl N-[(3S)-5-[4-[(3S)-3-(tert-butoxycarbonylamino)-2-oxo-3,4-dihydro-1H-1,5-benzodiazepine-5-carbonyl]benzoyl]-2-oxo-3,4-dihydro-1H-1,5-benzodiazepin-3-yl]carbamate (27.6 mg, 0.0403 mmol), 6-bromo-1-(chloromethyl)-2-methoxynaphthalene (25.3 mg, 0.0887 mmol), and cesium carbonate (39.4 mg, 0.121 mmol) where combined in DMF (2 mL) and stirred at room temperature for 16 h. The mixture was diluted with ethyl acetate, washed with water, brine and dried over anhydrous magnesium sulfate. Concentration gave an oil that was chromatographed over silica gel to give tert-butyl N-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-1-[4-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-3-(tert-butoxycarbonylamino)-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-3-yl]carbamate (31 mg, 65%) as a white foam.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationConcentration
  4. customgave an oil that
  5. customwas chromatographed over silica gel

Sources & evidence

ORD record
ord-c88dbb2d473c41b5bd7c0da3ad8487b0
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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