Acetyl chloride → (S)-N-[(2S,3S)-1-(4-acetyl-benzoyl)-5-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-2-methylamino-propionamide hydrochloride

HRID 1486038Notes

Reaction equation

HRID 1486038 reaction equation
C([Cl:4])(=O)C.C(O[C:10](=O)[N:11]([C@H:13]([C:15](=[O:55])[NH:16][C@H:17]1[C@H:23]([CH3:24])[N:22]([C:25](=[O:35])[C:26]2[CH:31]=[CH:30][C:29]([C:32](=[O:34])[CH3:33])=[CH:28][CH:27]=2)[C:21]2[CH:36]=[CH:37][CH:38]=[CH:39][C:20]=2[N:19]([CH2:40][C:41]2[C:50]3[C:45](=[C:46]([Br:51])[CH:47]=[CH:48][CH:49]=3)[CH:44]=[CH:43][C:42]=2[O:52][CH3:53])[C:18]1=[O:54])[CH3:14])C)(C)(C)C>CO>[ClH:4].[C:32]([C:29]1[CH:28]=[CH:27][C:26]([C:25]([N:22]2[C@@H:23]([CH3:24])[C@H:17]([NH:16][C:15](=[O:55])[C@@H:13]([NH:11][CH3:10])[CH3:14])[C:18](=[O:54])[N:19]([CH2:40][C:41]3[C:50]4[C:45](=[C:46]([Br:51])[CH:47]=[CH:48][CH:49]=4)[CH:44]=[CH:43][C:42]=3[O:52][CH3:53])[C:20]3[CH:39]=[CH:38][CH:37]=[CH:36][C:21]2=3)=[O:35])=[CH:31][CH:30]=1)(=[O:34])[CH3:33]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 90082508{(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-5-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester

Product 1

HCID 73388484(S)-N-[(2S,3S)-1-(4-acetyl-benzoyl)-5-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-2-methylamino-propionamide hydrochlorideYield 82%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Acetyl chloride (0.5 ml, 7.03 mmol) was added dropwise to a solution of {(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-5-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (40 mg, 0.52 mmol) in methanol at 0° C. and the reaction was allowed to warm to ambient temperature and stir for 2 h. The reaction was concentrated in vacuo and the residue was triturated with diethyl ether, filtered and dried to give (S)-N-[(2S,3S)-1-(4-acetyl-benzoyl)-5-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-2-methylamino-propionamide hydrochloride (30 mg, 82%). LR-MS [M+H+]672, 673

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe residue was triturated with diethyl ether
  3. filtrationfiltered
  4. customdried

Sources & evidence

ORD record
ord-ac85546c5efa40bc83b9bc58f6128692
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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