N-Hydroxysuccinimide suberic acid ester → (S)-di-tert-butyl 2-(3-((S)-1-tert-butoxy-6-(8-(2,5-dioxopyrrolidin-1-yloxy)-8-oxooctanamido)-1-oxohexan-2-yl)ureido)pentanedioate

HRID 56339

Reaction equation

HRID 56339 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([NH:14][C:15](=[O:34])[NH:16][C@@H:17]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH2:35]1[C:40](=[O:41])[N:39]([O:42][C:43]([CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][C:51](ON2C(=O)CCC2=O)=[O:52])=[O:44])[C:37](=[O:38])[CH2:36]1>CN(C=O)C>[C:10]([O:9][C:7](=[O:8])[C@@H:6]([NH:14][C:15](=[O:34])[NH:16][C@@H:17]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:51](=[O:52])[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46][CH2:45][C:43]([O:42][N:39]1[C:40](=[O:41])[CH2:35][CH2:36][C:37]1=[O:38])=[O:44])([CH3:13])([CH3:12])[CH3:11]

Participants

4

Reactant 2

HCID 100658N-Hydroxysuccinimide suberic acid esterHCID 251942251,5-Bis(1,1-dimethylethyl) N-((((1S)-5-amino-1-((1,1-dimethylethoxy)carbonyl)pentyl)amino)carbonyl)-L-glutamate

Product 1

HCID 86643493(S)-di-tert-butyl 2-(3-((S)-1-tert-butoxy-6-(8-(2,5-dioxopyrrolidin-1-yloxy)-8-oxooctanamido)-1-oxohexan-2-yl)ureido)pentanedioateYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of (S)-di-tert-butyl 2-(3-((S)-6-amino-1-tert-butoxy-1-oxohexan-2-yl)ureido)pentanedioate (0.488 g, 1.0 mmol) in DMF (20 mL) was added dropwise to a solution of suberic acid bis(N-hydroxysuccinimide ester) (1.47 g, 4.0 mmol) in DMF (80 mL) via a syringe pump. After 2 h, the solvent was evaporated under reduced pressure to give a residue, which was purified by flash chromatography over silica gel eluting with AcCN/DCM to give (S)-di-tert-butyl 2-(3-((S)-1-tert-butoxy-6-(8-(2,5-dioxopyrrolidin-1-yloxy)-8-oxooctanamido)-1-oxohexan-2-yl)ureido)pentanedioate (0.54 g, 73%). MS (ESI), 741.6 (M+H)+.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customto give a residue, which
  3. customwas purified by flash chromatography over silica gel eluting with AcCN/DCM

Sources & evidence

ORD record
ord-ab7d8ebce3a94a44975f03107e0e9cd0
Source dataset
uspto-grants-2016_09
Patent number
US09433594B2

Linked notes

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