N-Hydroxysuccinimide → HCID 117735922, compound

HRID 1482296Notes

Reaction equation

HRID 1482296 reaction equation
Cl.C(N=C=NCCCN(C)C)C.[CH:13]1[C:25]2[CH:24]([CH2:26][O:27][C:28]([NH:30][C@@H:31]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:32]([OH:34])=[O:33])=[O:29])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]=2[CH:16]=[CH:15][CH:14]=1.ON1C(=O)CCC1=O.[C:50]([S:54][S:55][CH2:56][CH:57](O)[C:58]([OH:60])=[O:59])([CH3:53])([CH3:52])[CH3:51]>CN(C)C=O.CN(C)C1C=CN=CC=1.C(O)=O>[CH:13]1[C:25]2[CH:24]([CH2:26][O:27][C:28]([NH:30][C@@H:31]([CH2:35][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[C:32]([O:34][CH:57]([CH2:56][S:55][S:54][C:50]([CH3:53])([CH3:52])[CH3:51])[C:58]([OH:60])=[O:59])=[O:33])=[O:29])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]=2[CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 80170N-HydroxysuccinimideHCID 978331Fmoc-phenylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 117736397HCID 117736397, compound

Product 1

HCID 117735922HCID 117735922, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 284Formic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI.HCl) (247 mg, 1.29 mmol) was added to a solution of (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-phenylpropanoic acid (Fmoc-Phe-OH) (500 mg, 1.29 mmol) and N-hydroxysuccinimide (HOSu) (149 mg, 1.29 mmol) in dimethylformamide (DMF) (4.5 ml) at room temperature under a nitrogen atmosphere, and the mixture was stirred at the same temperature for 18 hours. 3-(tert-Butyldisulfanyl)-2-hydroxypropanoic acid (Compound SP666) (100 mg, 0.475 mmol) and 4-dimethylaminopyridine (DMAP) (58.1 mg, 0.475 mmol) were added to the reaction solution (1.7 ml) at room temperature, and the mixture was stirred at the same temperature for 5 hours. Formic acid (18 μl) was added to the reaction solution, and the mixture was purified by reverse-phase silica gel chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution) to afford 2-(((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-phenylpropanoyl)oxy)-3-(tert-butyldisulfanyl)propanoic acid (Fmoc-Phe-tBuSSlac-OH) (Compound SP667) (110 mg, 40%).

Workup

  1. stirringthe mixture was stirred at the same temperature for 5 hours
  2. customthe mixture was purified by reverse-phase silica gel chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution)

Sources & evidence

ORD record
ord-33debc3f972b4ce78991b18f1aa8999b
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

Loading…