Diisopropylethylamine → (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-((R)-3-(((4-azidobenzyl)oxy) carbonyl) thiazolidine-4-carboxamido)hexanoic acid

HRID 1482276Notes

Reaction equation

HRID 1482276 reaction equation
[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[N:19]([C:22]1[CH:39]=[CH:38][C:25]([CH2:26][O:27][C:28]([N:30]2[C@H:34]([C:35]([OH:37])=O)[CH2:33][S:32][CH2:31]2)=[O:29])=[CH:24][CH:23]=1)=[N+:20]=[N-:21].[CH:40]1[C:52]2[CH:51]([CH2:53][O:54][C:55]([NH:57][C@@H:58]([CH2:62][CH2:63][CH2:64][CH2:65][NH2:66])[C:59]([OH:61])=[O:60])=[O:56])[C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:44]=2[CH:43]=[CH:42][CH:41]=1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(O)=O>[CH:49]1[C:50]2[CH:51]([CH2:53][O:54][C:55]([NH:57][C@@H:58]([CH2:62][CH2:63][CH2:64][CH2:65][NH:66][C:35]([C@@H:34]3[CH2:33][S:32][CH2:31][N:30]3[C:28]([O:27][CH2:26][C:25]3[CH:24]=[CH:23][C:22]([N:19]=[N+:20]=[N-:21])=[CH:39][CH:38]=3)=[O:29])=[O:37])[C:59]([OH:61])=[O:60])=[O:56])[C:52]3[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:45]=2[CH:46]=[CH:47][CH:48]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 7010557(2S)-6-amino-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)hexanoic acidHCID 117735920HCID 117735920, compound

Product 1

HCID 117736227(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-((R)-3-(((4-azidobenzyl)oxy) carbonyl) thiazolidine-4-carboxamido)hexanoic acidYield 51.3%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 6228DimethylformamideSolvent2×

Procedure

4-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) (2.85 g, 10.3 mmol) was added to a solution of (R)-3-(((4-azidobenzyl)oxy)carbonyl)thiazolidine-4-carboxylic acid (Acbz-Thz-OH) (Compound SP610) (3.17 g, 10.3 mmol) in dimethylformamide (DMF) (17.0 ml) at room temperature under a nitrogen atmosphere, and the mixture was stirred at the same temperature for 1 hour and 30 minutes. A solution of (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-aminohexanoic acid (Fmoc-Lys-OH) hydrochloride (4.16 g, 10.3 mmol) and diisopropylethylamine (DIPEA) (2.69 ml, 15.4 mmol) in dimethylformamide (DMF) (17 ml) was added to the reaction solution at room temperature, and the mixture was stirred at the same temperature for 4 hours. Formic acid (1.9 ml) 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 (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-6-((R)-3-(((4-azidobenzyl)oxy) carbonyl) thiazolidine-4-carboxamido)hexanoic acid (Fmoc-Lys(Acbz-Thz)-OH) (Compound SP611) (3.48 g, 51%).

Workup

  1. stirringthe mixture was stirred at the same temperature for 4 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-f7ea824582e24280877b36dc68f556ea
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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