tert-Butyl mercaptan → HCID 89668271, compound

HRID 1482224Notes

Reaction equation

HRID 1482224 reaction equation
C(CCP(CCC(O)=O)CCC(O)=O)(O)=O.[C:17]([O:21][C:22]([NH:24][C@@H:25]([CH2:36][CH2:37][C:38]([NH:40][C@@H:41]([CH2:47]S)[C:42]([O:44][CH2:45][CH3:46])=[O:43])=[O:39])[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])=[O:23])([CH3:20])([CH3:19])[CH3:18].C(S)(C)(C)C>CN(C=O)C>[C:17]([O:21][C:22]([NH:24][C@@H:25]([CH2:36][CH2:37][C:38]([NH:40][C@@H:41]([CH3:47])[C:42]([O:44][CH2:45][CH3:46])=[O:43])=[O:39])[C:26]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:27])=[O:23])([CH3:20])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 6387tert-Butyl mercaptanHCID 119411Tris(2-carboxyethyl)phosphineHCID 89668337(S)-benzyl 2-((tert-butoxycarbonyl)amino)-5-(((R)-1-ethoxy-3-mercapto-1-oxopropan-2-yl)amino)-5-oxopentanoate2×

Product 1

HCID 89668271HCID 89668271, compoundYield 97.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 0.4 M aqueous tris(2-carboxyethyl)phosphine (TCEP) solution (0.428 ml, 0.171 mmol) was added to a solution of (S)-benzyl 2-((tert-butoxycarbonyl)amino)-5-(((R)-1-ethoxy-3-mercapto-1-oxopropan-2-yl)amino)-5-oxopentanoate (Compound 3a) (20.0 mg, 0.0427 mmol) in DMF (0.8 ml), and the mixture was stirred at room temperature for 15 minutes. tBuSH (0.0144 ml, 0.128 mmol) and a 1 M aqueous 2,2′-azobis-2-(2-imidazolin-2-yl)propane (VA-044) solution (0.0427 ml, 0.0427 mmol) were then added and the mixture was stirred at 50° C. for 2.5 hours. The reaction solution was then diluted by adding water, and subsequent purification by reverse-phase silica gel column chromatography (10 mM aqueous ammonium acetate solution/methanol=70/30→20/80) afforded (S)-benzyl 2-((tert-butoxycarbonyl)amino)-5-(((S)-1-ethoxy-1-oxopropan-2-yl)amino)-5-oxopentanoate (Compound 3b) (18.1 mg, 97%).

Workup

  1. stirringthe mixture was stirred at 50° C. for 2.5 hours
  2. additionThe reaction solution was then diluted
  3. additionby adding
  4. customwater, and subsequent purification by reverse-phase silica gel column chromatography (10 mM aqueous ammonium acetate solution/methanol=70/30→20/80)

Sources & evidence

ORD record
ord-b73e1c8bdb8f4e8d8b247e03f6c3faf5
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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