Hydrochloric Acid → HCID 89668615, compound

HRID 1482332Notes

Reaction equation

HRID 1482332 reaction equation
[C:1](=[O:23])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]=[N+:11]=[N-:12])=[CH:6][CH:5]=1.Cl.[C:25]([NH:42][C@H:43]([C:49]([OH:51])=[O:50])[CH2:44][CH2:45][CH2:46][CH2:47][NH2:48])([O:27][CH2:28][CH:29]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]2[C:30]1=[CH:31][CH:32]=[CH:33][CH:34]=2)=[O:26].C(=O)(O)[O-].[Na+].Cl>CN(C=O)C>[CH:31]1[C:30]2[CH:29]([CH2:28][O:27][C:25]([NH:42][C@@H:43]([CH2:44][CH2:45][CH2:46][CH2:47][NH:48][C:1]([O:2][CH2:3][C:4]3[CH:5]=[CH:6][C:7]([N:10]=[N+:11]=[N-:12])=[CH:8][CH:9]=3)=[O:23])[C:49]([OH:51])=[O:50])=[O:26])[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:35]=2[CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 11809184HCID 11809184, compoundHCID 11858928(2S)-6-amino-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)hexanoic acid hydrochloride

Product 1

HCID 89668615HCID 89668615, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

4-Azidobenzyl (4-nitrophenyl) carbonate synthesized by the method described in the literature (Bioconjugate Chem. 2008, 19, 714) (Compound tk32) (3.46 g, 11.0 mmol) was added to a suspension of Fmoc-lysine hydrochloride (Compound tk31) (4.9 g, 12.10 mmol) and sodium bicarbonate (2.77 g, 33.0 mmol) in DMF (22 mL) under ice-cooling. The reaction mixture was stirred at 25° C. for 8 hours and 1 N hydrochloric acid was then added, followed by extraction with ethyl acetate. The organic phase was washed with brine three times and dried over sodium sulfate. Following concentration under reduced pressure, the resulting 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)carbonyl)amino)-6-((((4-azidobenzyl)oxy)carbonyl)amino)hexanoic acid (Compound SP661) (5.5 g, 92%).

Workup

  1. temperaturecooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic phase was washed with brine three times
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentration under reduced pressure
  6. customthe resulting 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-29ee889a8cc24155a751cf82263004bc
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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