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

HRID 2185427Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2185427
ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:23]([O:27][C:28]([N:30]1[CH2:37][C@H:36]([CH2:38][NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:35][C@H:31]1[C:32]([OH:34])=O)=[O:29])([CH3:26])([CH3:25])[CH3:24].[N:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:50]=[C:49]([NH:57][C:58](=[O:89])[C@@H:59]2[CH2:63][C@@H:62]([NH:64][C:65](=[O:76])[C@H:66]([OH:75])[CH2:67][CH2:68][C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)[CH2:61][N:60]2C(=O)[C@H]2C[C@H](NC(=O)CN)CN2)[CH:48]=1>ClCCl.C(Cl)(Cl)Cl.C(N(CC)CC)C>[N:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:50]=[C:49]([NH:57][C:58](=[O:89])[C@@H:59]2[CH2:63][C@@H:62]([NH:64][C:65](=[O:76])[C@H:66]([OH:75])[CH2:67][CH2:68][C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)[CH2:61][N:60]2[C:32](=[O:34])[C@@H:31]2[CH2:35][C@@H:36]([CH2:38][NH:39][C:40]([O:42][C:43]([CH3:45])([CH3:44])[CH3:46])=[O:41])[CH2:37][N:30]2[C:28]([O:27][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:29])[CH:48]=1

Komponenten

8

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341428trans-4-Glycylamino-D-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-proline 3-QuinolylamideHCID 213415491-(1,1-Dimethylethyl) (2S,4S)-4-((((1,1-dimethylethoxy)carbonyl)amino)methyl)-1,2-pyrrolidinedicarboxylate

Produkt 1

HCID 21341551N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycarbonylaminomethyl)-L-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-Proline 3-QuinolylamideAusbeute 78,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6212ChloroformLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

Triethylamine (36 μL), 1-hydroxybenzotriazole (9 mg) and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (49 mg) were added to a stirred solution of N-tert-butoxycarbonyl-trans-4-(N-tert-butoxycarbonylamino)methyl-L-Proline (D, 80 mg) and trans-4-((R)-2-hydroxy-4-phenylbutrylamino)-L-proline 3-quinolylamide (CompoundDlol (H), 97 mg) in dichloromethane (4 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 silica gel column chromatography (chloroform:methanol=100:1, v/v) to give the title compound (97 mg) as a colorless foam: 1H NMR (400 MHz, CDCl3) δ 1.41 (s, 9H), 1.45 (s, 9H), 1.97-2.31 (m, 6H), 2.71 (m, 1H), 2.74 (m, 2H), 3.21 (m, 2H), 3.64 (m, 2H), 3.79 (m, 1H), 3.91 (m, 1H), 4.49-4.55 (m, 2H), 4.79 (m, 1H), 4.93 (m, 2H), 7.17-7.52 (m, 9H), 8.49 (s, 1H), 8.57 (s, 1H), and 10.2 (m, 1H).

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 silica gel column chromatography (chloroform

Quellen und Nachweise

ORD-Eintrag
ord-3468e205b1424d6892099f289a6a6645
Quelldatensatz
uspto-grants-2002_06
Patentnummer
US06399629B1

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