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

HRID 2185429Notes

Reaction equation

HRID 2185429 reaction equation
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

Participants

8

Reactant 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

Product 1

HCID 21341470N-tert-Butoxycarbonyl-4-[2-(tert-Butoxycarbonylamino)ethyl]-L-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-Proline 3-QuinolylamideYield 46.3%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-cce93e1a6c0348b19779d1f810ca20b2
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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