Piperidine → Cypate Lys

HRID 1879604

Reaction equation

HRID 1879604 reaction equation
[NH:1](C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][CH2:5][CH2:6][NH2:7].N1CCCCC1.[CH3:34][C:35]1([CH3:80])[C:47](/[CH:48]=[CH:49]/[CH:50]=[CH:51]/[CH:52]=[CH:53]/[CH:54]=[C:55]2\[C:56]([CH3:74])([CH3:73])[C:57]3[C:58]4[CH:59]=[CH:60][CH:61]=[CH:62][C:63]=4[CH:64]=[CH:65][C:66]=3[N:67]\2[CH2:68][CH2:69][C:70]([OH:72])=[O:71])=[N+:46]([CH2:75][CH2:76][C:77]([OH:79])=[O:78])[C:45]2[CH:44]=[CH:43][C:42]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[C:36]1=2.[Br-:81].C1C=CC2N(O)N=NC=2C=1.CC(C)N=C=NC(C)C>CN(C=O)C>[CH3:34][C:35]1([CH3:80])[C:47](/[CH:48]=[CH:49]/[CH:50]=[CH:51]/[CH:52]=[CH:53]/[CH:54]=[C:55]2\[C:56]([CH3:73])([CH3:74])[C:57]3[C:58]4[CH:59]=[CH:60][CH:61]=[CH:62][C:63]=4[CH:64]=[CH:65][C:66]=3[N:67]\2[CH2:68][CH2:69][C:70]([OH:72])=[O:71])=[N+:46]([CH2:75][CH2:76][C:77]([OH:79])=[O:78])[C:45]2[CH:44]=[CH:43][C:42]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[C:36]1=2.[Br-:81].[NH2:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][CH2:5][CH2:6][NH2:7]

Participants

7

Reactant 5

HCID 8082PiperidineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7010557(2S)-6-amino-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)hexanoic acidHCID 10963571Cypate

Product 1

HCID 137227855Cypate Lys

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Fmoc-Lys was attached to Rink amide resin (60 mg, 0.0366 mmol) and the Fmoc was deprotected by piperidine in DMF (20%). A solution of Cypate (129 mg, 5 equiv), HOBT(24.7 mg), and DIC (11.5 mg, 2.5 equiv) in DMF (3 mL) was added into the resin and swirled overnight. After filtered, the resin was washed with DMF and DCM, cleaved with TFA/H2O (95:5) for 3 h, filtered, concentrated, and dried. The crude product was dissolved in 20 mL DCM and added dropwise into a stirred solution of PyBOP (38 mg), HOBT (9.9 mg), and DIEA (18.9 mg) in DCM/DMF(195:5, 200 mL) and the resulting mixture was stirred overnight, concentrated, and purified by HPLC to afforded 1.5 mg of the desired product.

Workup

  1. filtrationAfter filtered
  2. washthe resin was washed with DMF and DCM
  3. waitcleaved with TFA/H2O (95:5) for 3 h
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customdried
  7. dissolutionThe crude product was dissolved in 20 mL DCM
  8. additionadded dropwise into a stirred solution of PyBOP (38 mg), HOBT (9.9 mg), and DIEA (18.9 mg) in DCM/DMF(195:5, 200 mL)
  9. concentrationconcentrated
  10. custompurified by HPLC

Sources & evidence

ORD record
ord-9b87c923962b4622a9730cedf434c70f
Source dataset
uspto-grants-2012_11
Patent number
US08318133B2

Linked notes

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