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1-Hydroxybenzotriazole → N-tert-Butoxycarbonyl-4-[2-(tert-Butoxycarbonylamino)ethyl]-L-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-Proline 3-Quinolylamide

HRID 2185429
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Reaktionsgleichung

Reaktionsgleichung von HRID 2185429
ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:23]([O:27][C:28]([N:30]1[CH2:37][CH:36]([CH2:38][CH2:39][NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:35][C@H:31]1[C:32](O)=[O:33])=[O:29])([CH3:26])([CH3:25])[CH3:24].[N:48]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=[C:50]([NH:58][C:59](=[O:78])[C@@H:60]2[CH2:64][C@@H:63]([NH:65][C:66](=[O:77])[C@H:67]([OH:76])[CH2:68][CH2:69][C:70]3[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=3)[CH2:62][NH:61]2)[CH:49]=1>ClCCl.C(Cl)(Cl)Cl.C(N(CC)CC)C>[N:48]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=[C:50]([NH:58][C:59](=[O:78])[C@@H:60]2[CH2:64][C@@H:63]([NH:65][C:66](=[O:77])[C@H:67]([OH:76])[CH2:68][CH2:69][C:70]3[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=3)[CH2:62][N:61]2[C:32](=[O:33])[C@@H:31]2[CH2:35][CH:36]([CH2:38][CH2:39][NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][N:30]2[C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:29])[CH:49]=1
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Komponenten

8

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341500N-tert-Butoxycarbonyl-4-(N-tert-Butoxycarbonyl-2-Aminoethyl)-L-ProlineHCID 59895122trans-4-((R)-2-Hydroxy-4-Phenylbutrylamino)-L-Proline 3-Quinolylamide

Produkt 1

HCID 21341470
N-tert-Butoxycarbonyl-4-[2-(tert-Butoxycarbonylamino)ethyl]-L-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-Proline 3-Quinolylamide
Ausbeute 46,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6212ChloroformLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

Triethylamine (21 μL), 1-hydroxybenzotriazole (9 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (28 mg) were added to a solution of N-tert-butoxycarbonyl-4-[2-(tert-butoxycarbonylamino)ethyl]-L-Proline (48 mg) and trans-4-((R)-2-hydroxy-4-phenylbutyrylamino)-L-proline 3-quinolylamide (Compound D101 (H), 56 mg) in dichloromethane (3 mL) at 0° C. The mixture was stirred at room temperature overnight. The reaction mixture was diluted with chloroform and washed with saturated sodium hydrogen carbonate and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by preparative silica gel thin layer chromatography (chloroform:methanol=12:1, v/v) to give the title compound (47 mg) as a colorless foam: 1H NMR (400 MHz, CDCl3) δ 1.40 (s, 9H), 1.48 (s, 9H), 1.71 (m, 2H), 1.99 (m, 1H), 2.13-2.51 (m, 6H), 2.75 (m, 2H), 3.16 (m, 2H), 3.63 (m, 1H), 3.73 (m, 1H), 3.87 (m, 1H), 3.90 (m, 1H), 4.38 (m, 1H), 4.53 (m, 1H), 4.80 (m, 1H), 4.82 (m, 1H), 5.50 (m, 1H), 7.15-7.64 (m, 9H), 7.68 (m, 1H), and 8.54 (m, 2H).

Aufarbeitung

  1. washwashed with saturated sodium hydrogen carbonate and brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. customevaporated in vacuo
  4. customThe residue was purified by preparative silica gel thin layer chromatography (chloroform

Quellen und Nachweise

ORD-Eintrag
ord-cce93e1a6c0348b19779d1f810ca20b2
Quelldatensatz
uspto-grants-2002_06
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US06399629B1

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