Diisopropylethylamine → HCID 131724516, compound

HRID 1835565Notes

Reaction equation

HRID 1835565 reaction equation
[NH:1]([C:14]([O:16]CC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=1.[CH:31]1[CH:36]=[CH:35][C:34]([C:37](Cl)([C:44]2C(Cl)=CC=CC=2)C2C=CC=CC=2)=[CH:33][CH:32]=1.[CH:52]([N:55](C(C)C)CC)(C)C.C(N(C)[C@@H](C(O)=O)CC1C=CC=CC=1)(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.N[C@@H](C(O)=O)CC1C=CC(Cl)=CC=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[NH:55]([CH3:52])[C@@H:44]([C:14]([NH:1][C@@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([Cl:10])=[CH:8][CH:9]=1)=[O:16])[CH2:37][C:34]1[CH:35]=[CH:36][CH:31]=[CH:32][CH:33]=1

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 945242-Chlorotrityl chlorideHCID 667429(2R)-2-amino-3-(4-chlorophenyl)propanoic acidHCID 978357(2R)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}(methyl)amino)-3-phenylpropanoic acidHCID 162131634-Chloro-N-{[(9H-fluoren-9-yl)methoxy]carbonyl}-D-phenylalanineHCID 22988621HOBt HBTU

Product 1

HCID 131724516HCID 131724516, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Fmoc-(D)Phe(4-Cl)-OH (844 mg, 2 mmol) was coupled to 2-chlorotritylchloride resin (Alexis, 0.75 g, 1 mmol) in the presence of diisopropylethylamine (2 mmol 0.35 ml) in DMF (8 ml) by an automated procedure on an Applied Biosystems 430A peptide synthesiser. After 1 hour at ambient temperature, the resin was filtered and washed with DMF. After deprotection with 20% piperidine in DMF (two treatments with 15 ml), the resin was thoroughly washed with DMF (5×10 ml). Fmoc-NMe(D)Phe-OH (803 mg, 2 mmol) was coupled to the resin-bound H-(D)Phe(4-Cl) by the standard HBTU/HOBt chemistry similar to that used in example 3. After extensive washing with DMF, the deprotection procedure described above was repeated to give H-NMe(D)Phe-(D)Phe(4-Cl)-resin. Fmoc-(D)Lys(BOC)-OH (938 mg, 2 mmol) was coupled by the HATU procedure (see J Chem Soc. Chem Comm. 1994, 201). After 1 hour at ambient temperature the resin as filtered and washed with DMF. After deprotection and extensive washing with DMF, cyclohexane carboxylic acid (256 mg, 2 mmol) was coupled by standard HBTU/HOBt chemistry similar to that described above to the resin bound tripeptide to give cyclohexyl-(D)Lys(BOC)-NMe(D)Phe-(D)Phe(4-Cl) on the resin. The peptide resin was collected and washed with methanol and dried, in vacuo, at 50° C. Yield 1.337 g (gain 587 mg).

Workup

  1. filtrationthe resin was filtered
  2. washwashed with DMF
  3. washAfter deprotection with 20% piperidine in DMF (two treatments with 15 ml), the resin was thoroughly washed with DMF (5×10 ml)
  4. washAfter extensive washing with DMF

Sources & evidence

ORD record
ord-47b327b03b7c4ad1b14d27e6bfa0619d
Source dataset
uspto-grants-2004_08
Patent number
US06770627B1

Reaction notes

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