Bromoacetonitrile → (S)-cyanomethyl 2-((tert-butoxycarbonyl)amino)-6-((R)-2-((tert-butoxycarbonyl)amino)-3-(tert-butyldisulfanyl)propanamido)hexanoate

HRID 1482314Notes

Reaction equation

HRID 1482314 reaction equation
[CH:1]([N:4](CC)C(C)C)(C)[CH3:2].BrCC#N.[C:14]([O:18][C:19]([NH:21][C@@H:22]([CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:31](=[O:48])[C@@H:32]([NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:33][S:34][S:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:23]([OH:25])=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15]>C(#N)C>[C:14]([O:18][C:19]([NH:21][C@@H:22]([CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:31](=[O:48])[C@@H:32]([NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:33][S:34][S:35][C:36]([CH3:38])([CH3:39])[CH3:37])[C:23]([O:25][CH2:2][C:1]#[N:4])=[O:24])=[O:20])([CH3:15])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 81531DiisopropylethylamineHCID 89668377(S)-2-((tert-butoxycarbonyl)amino)-6-((R)-2-((tert-butoxycarbonyl)amino)-3-(tert-butyldisulfanyl)propanamido)hexanoic acid2×

Product 1

HCID 89668376(S)-cyanomethyl 2-((tert-butoxycarbonyl)amino)-6-((R)-2-((tert-butoxycarbonyl)amino)-3-(tert-butyldisulfanyl)propanamido)hexanoateYield 78%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N,N-diisopropylethylamine (0.073 mL, 0.421 mmol) and subsequently bromoacetonitrile (0.080 mL, 1.15 mmol) were added to a solution of (S)-2-((tert-butoxycarbonyl)amino)-6-((R)-2-((tert-butoxycarbonyl)amino)-3-(tert-butyldisulfanyl)propanamido)hexanoic acid (Compound 52) (206 mg, 0.383 mmol) in acetonitrile (0.3 mL) at room temperature under a nitrogen atmosphere. The reaction mixture was stirred at the same temperature for 5 hours and then concentrated under reduced pressure, and the resulting crude product was purified by normal-phase silica gel column chromatography (hexane/ethyl acetate) to afford (S)-cyanomethyl 2-((tert-butoxycarbonyl)amino)-6-((R)-2-((tert-butoxycarbonyl)amino)-3-(tert-butyldisulfanyl)propanamido)hexanoate (Compound 53) (172.2 mg, 78%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customthe resulting crude product was purified by normal-phase silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-904e7ea596434240a61f081c512943b7
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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