Hydrochloric Acid → HCID 89668555, compound

HRID 1482272Notes

Reaction equation

HRID 1482272 reaction equation
[CH2:1]([O:4][C:5]([NH:7][C@@H:8]([CH2:12][S:13][S:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:9]([OH:11])=O)=[O:6])[CH:2]=[CH2:3].ON1C(=O)CCC1=O.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.[NH:48]([C:58]([O:60][CH2:61][CH:62]1[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[C:68]2[C:63]1=[CH:64][CH:65]=[CH:66][CH:67]=2)=[O:59])[C@H:49]([C:55]([OH:57])=[O:56])[CH2:50][CH2:51][CH2:52][CH2:53][NH2:54].Cl>ClCCl>[CH:64]1[C:63]2[CH:62]([CH2:61][O:60][C:58]([NH:48][C@@H:49]([CH2:50][CH2:51][CH2:52][CH2:53][NH:54][C:9](=[O:11])[C@@H:8]([NH:7][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6])[CH2:12][S:13][S:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:55]([OH:57])=[O:56])=[O:59])[C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[C:68]=2[CH:67]=[CH:66][CH:65]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 80170N-HydroxysuccinimideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7010557(2S)-6-amino-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)hexanoic acidHCID 714142233-(tert-Butyldisulfanyl)-N-{[(prop-2-en-1-yl)oxy]carbonyl}-L-alanine

Product 1

HCID 89668555HCID 89668555, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (R)-2-(allyloxycarbonylamino)-3-(tert-butyldisulfanyl)propanoic acid (Alloc-Cys(StBu)-OH) (1.9 g, 6.48 mmol) and N-hydroxysuccinimide (0.745 g, 6.48 mmol) in dichloromethane (10 ml) was cooled to 0° C., after which 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl, 1.24 g, 6.48 mmol) was added and the reaction solution was stirred at room temperature for 20 hours. After 20 hours, the reaction solution was cooled to 0° C., after which N,N-diisopropylethylamine (2.49 ml, 14.25 mmol) and Fmoc-Lys-OH (2.39 g, 6.48 mmol) were added and the reaction solution was stirred at room temperature for 2 hours. Dichloromethane and 1 M hydrochloric acid were added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with 25 wt % brine, the resulting solution was concentrated under reduced pressure, and the concentration residue was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution) to afford (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-((R)-2-(allyloxycarbonylamino)-3-(tert-butyldisulfanyl)propanamido)hexanoic acid (Compound 150a, Fmoc-Lys(Alloc-Cys(StBu))-OH) (2.66 g, 64%).

Workup

  1. waitAfter 20 hours
  2. temperaturethe reaction solution was cooled to 0° C.
  3. stirringthe reaction solution was stirred at room temperature for 2 hours
  4. extractionfollowed by extraction with dichloromethane
  5. washThe organic layer was washed with 25 wt % brine
  6. concentrationthe resulting solution was concentrated under reduced pressure
  7. customthe concentration residue was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution)

Sources & evidence

ORD record
ord-f4ef6baf89d24f7ebd780818c5cd2fdf
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

Loading…