1-Hydroxybenzotriazole → N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycabonylglycylamino)-L-Proline 4-Phenylbenzylamide

HRID 2185454Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2185454
ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.FC(F)(F)C(O)=O.[C:30]1([C:36]2[CH:43]=[CH:42][C:39]([CH2:40][NH2:41])=[CH:38][CH:37]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[C:44]([O:48][C:49]([NH:51][CH2:52][C:53]([NH:55][C@H:56]1[CH2:60][N:59]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C@H:58]([C:68](O)=[O:69])[CH2:57]1)=[O:54])=[O:50])([CH3:47])([CH3:46])[CH3:45]>ClCCl.C(N(CC)CC)C>[C:30]1([C:36]2[CH:37]=[CH:38][C:39]([CH2:40][NH:41][C:68](=[O:69])[C@@H:58]3[CH2:57][C@@H:56]([NH:55][C:53](=[O:54])[CH2:52][NH:51][C:49]([O:48][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:50])[CH2:60][N:59]3[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])=[CH:42][CH:43]=2)[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Komponenten

7

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341559trans-4-(N-tert-butoxycarbonylglycyl)amino-N-tert-butoxycarbonyl-L-prolineHCID 224587204-Phenylbenzylamine trifluoroacetate

Produkt 1

HCID 131723254N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycabonylglycylamino)-L-Proline 4-PhenylbenzylamideAusbeute 83,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

Triethylamine (130 μL), 1-hydroxybenzotriazole (59 mg), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (89 mg) were added to a solution of the 4-phenylbenzylamine trifluoroacetate (B, 126 mg) and trans-4-(N-tert-butoxycarbonylglycylamino)-N-tert-butoxycarbonyl-L-proline (Compound D103 (B), 150 mg) in dichloromethane (10 mL) at 0° C. The mixture was stirred at room temperature for 16 hr and concentrated in vacuo. The residue was diluted with ethyl acetate and washed with 1 N hydrochloric acid, water, saturated sodium hydrogen carbonate, and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (chloroform then chloroform:methanol=99:1 to 98:2, v/v) to give the title compound (178 mg) as a colorless foam:1H NMR (400 MHz, CDCl3) δ 1.45 (s, 18H), 1,67 (s, 2H), 2.01 (brs, 1H), 2.64 (br s, 1H), 3.27 (br s, 1H), 3.68-3.81 (m, 3H), 4.23-4.70 (m, 3H), 5.17 (br s, 1H), 6.43 (br s, 1H), 7.32-7.36 (m, 3H), 7.44 (t, J=7.6 Hz, 2H), and 7.53-7.57 (m, 4H).

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with 1 N hydrochloric acid, water, saturated sodium hydrogen carbonate, and brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (chloroform

Quellen und Nachweise

ORD-Eintrag
ord-156795b7c15948808f2181f6e80bc2d2
Quelldatensatz
uspto-grants-2002_06
Patentnummer
US06399629B1

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