Urea → Trityl-leucine amide

HRID 325055

Reaktionsgleichung

Reaktionsgleichung von HRID 325055
[NH2:1][C:2](N)=[O:3].N[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CNC(=O)[C@H:15]([CH2:17][CH:18]([CH3:20])[CH3:19])N.C[C:23]1[CH:36]=[CH:35][C:26]([CH:27]([NH2:34])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C.C(OC(N[C@H](C(O)=O)CC(C)C)=O)(C)(C)C.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C>ClCCl.CN(C)C=O>[C:27]([NH:34][C@H:15]([C:2]([NH2:1])=[O:3])[CH2:17][CH:18]([CH3:20])[CH3:19])([C:26]1[CH:25]=[CH:24][CH:23]=[CH:36][CH:35]=1)([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Komponenten

12

Edukt 9

HCID 1176UreaHCID 6115AnilineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 27342954-MethylbenzhydrylamineHCID 11672684(2S)-2-amino-N,4-dimethylpentanamideHCID 178435178HCID 178435178, Verbindung2×

Produkt 1

HCID 131722528Trityl-leucine amide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In the preparation of the urea of aniline and leucine methyl amide, 100 mg of p-methylbenzhydrylamine (MBHA) resin (0.81 meq/g, 100-200 mesh) was contained within a sealed polypropylene mesh packet as used in simultaneous multiple synthesis as described in Houghten, (Proc. Natl. Acad. Sci. USA 82:5131, 1985). Following neutralization (1 min) with 5% diisopropylethylamine (DIEA) in dichloromethane (DCM) (3×5 ml), the resin was washed with DCM (3×5 ml). The resin packet was added to a solution of tert-butyloxycarbonyl-L-leucine (Boc-Leu) (111 mg, 0.48 meq) and 1-hydroxybenzotriazole (65 mg, 0.48 meq) in dimethylformamide (DMF) (2.4 ml) in a 10 ml polypropylene bottle. Following addition of 2.4 ml 0.2 M diisopropylcarbodiimide (DICI) in DMF, the resin was shaken on a reciprocation shaker for 1.5 h. The resin was then washed with DMF (3×5 ml) and DCM (3×5 ml). The Boc protecting group was then removed by treatment with 55% trifluoroacetic acid in DCM for 30 min. The resin was then washed with DCM (2×5 ml), isopropanol (IPA, 3×5 ml), DCM (3×5 ml), neutralized with 5% DIEA in DCM (3×5 ml), and washed with DCM (2×5 ml). The resin packet was then shaken overnight (16 h) in 5 ml of 0.1 M trityl chloride in DCM/DMF (9:1) in the presence of DIEA. Completeness of the trityl coupling was verified using the bromophenol blue color test as described in Krchnak et al., (Coll. Czech. Chem. Commun. 53:2542, 1988), and repeated as necessary.

Aufarbeitung

  1. customas used in simultaneous multiple synthesis
  2. customneutralization (1 min)
  3. washthe resin was washed with DCM (3×5 ml)
  4. washThe resin was then washed with DMF (3×5 ml) and DCM (3×5 ml)
  5. customThe Boc protecting group was then removed by treatment with 55% trifluoroacetic acid in DCM for 30 min
  6. washThe resin was then washed with DCM (2×5 ml), isopropanol (IPA, 3×5 ml), DCM (3×5 ml)
  7. washwashed with DCM (2×5 ml)
  8. stirringThe resin packet was then shaken overnight (16 h) in 5 ml of 0.1 M trityl chloride in DCM/DMF (9:1) in the presence of DIEA

Quellen und Nachweise

ORD-Eintrag
ord-cb3df3e517754ba0b12c0e3c0f6241a0
Quelldatensatz
uspto-grants-2001_04
Patentnummer
US06221913B1

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