Acetyl chloride → (3S)-3-amino-1-[4-[(3S)-3-amino-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-2,3-dihydro-1,5-benzodiazepin-4-one dihydrochloride

HRID 1481939Notes

Reaction equation

HRID 1481939 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([CH2:12][N:13]1[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17]([C:24](=[O:67])[C:25]3[CH:30]=[CH:29][C:28]([C:31]([N:33]4[C:39]5[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=5[N:37]([CH2:44][C:45]5[C:54]6[C:49](=[CH:50][C:51]([Br:55])=[CH:52][CH:53]=6)[CH:48]=[CH:47][C:46]=5[O:56][CH3:57])[C:36](=[O:58])[C@@H:35]([NH:59]C(OC(C)(C)C)=O)[CH2:34]4)=[O:32])=[CH:27][CH:26]=3)[CH2:16][C@H:15]([NH:68]C(=O)OC(C)(C)C)[C:14]1=[O:76])=[C:7]([O:77][CH3:78])[CH:6]=[CH:5]2.C([Cl:82])(=O)C>CO>[ClH:82].[ClH:82].[NH2:59][C@H:35]1[CH2:34][N:33]([C:31](=[O:32])[C:28]2[CH:27]=[CH:26][C:25]([C:24]([N:17]3[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[N:13]([CH2:12][C:8]4[C:9]5[C:4](=[CH:3][C:2]([Br:1])=[CH:11][CH:10]=5)[CH:5]=[CH:6][C:7]=4[O:77][CH3:78])[C:14](=[O:76])[C@@H:15]([NH2:68])[CH2:16]3)=[O:67])=[CH:30][CH:29]=2)[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[N:37]([CH2:44][C:45]2[C:54]3[C:49](=[CH:50][C:51]([Br:55])=[CH:52][CH:53]=3)[CH:48]=[CH:47][C:46]=2[O:56][CH3:57])[C:36]1=[O:58]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 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]carbamate

Product 1

HCID 90220955(3S)-3-amino-1-[4-[(3S)-3-amino-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-2,3-dihydro-1,5-benzodiazepin-4-one dihydrochlorideYield 98.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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, 0.026 mmol) and acetyl chloride (9.3 μL, 0.131 mmol) were combined in MeOH (2 mL) and stirred at room temperature for 16 h. The mixture was concentrated to give (3S)-3-amino-1-[4-[(3S)-3-amino-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-2,3-dihydro-1,5-benzodiazepin-4-one dihydrochloride as a white solid (27 mg, 98%) that was used without further purification.

Workup

  1. concentrationThe mixture was concentrated

Sources & evidence

ORD record
ord-acef2d0fd33b4413a91640839842f6c2
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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