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

HRID 2185411Notes

Reaction equation

HRID 2185411 reaction equation
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]([NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][C@H:31]1[C:32]([OH:34])=O)=[O:29])([CH3:26])([CH3:25])[CH3:24].[N:46]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:49]=[C:48]([NH:56][C:57](=[O:76])[C@@H:58]2[CH2:62][C@@H:61]([NH:63][C:64](=[O:75])[C@H:65]([OH:74])[CH2:66][CH2:67][C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)[CH2:60][NH:59]2)[CH:47]=1>ClCCl.C(N(CC)CC)C>[N:46]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:49]=[C:48]([NH:56][C:57](=[O:76])[C@@H:58]2[CH2:62][C@@H:61]([NH:63][C:64](=[O:75])[C@H:65]([OH:74])[CH2:66][CH2:67][C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)[CH2:60][N:59]2[C:32](=[O:34])[C@@H:31]2[CH2:35][C@@H:36]([NH:38][C:39]([O:41][C:42]([CH3:44])([CH3:43])[CH3:45])=[O:40])[CH2:37][N:30]2[C:28]([O:27][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:29])[CH:47]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341545(4R)-1-Boc-4-(Boc-amino)-L-prolineHCID 59895122trans-4-((R)-2-Hydroxy-4-Phenylbutrylamino)-L-Proline 3-Quinolylamide

Product 1

HCID 21341547N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycarbonylamino)-L-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-Proline 3-Quinolylamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Triethylamine (30 μL), 1-hydroxybenzotriazole (28 mg), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (42 mg) were added to a cold (0° C.) stirred solution of N-tert-butoxycarbonyl-trans-4-(N-tert-butoxycarbonylamino)-L-proline (O, 76 mg) and trans-4-((R)-2-hydroxy-4-phenylbutyrylamino)-L-proline 3-quinolylamide(H, 76 mg) in dichloromethane (10 mL). The mixture was stirred at room temperature for 16.5 hr and evaporated 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 evaporated in vacuo. The residue was purified by preparative thin layer chromatography (Whatman, PLK5F Silica Gel 50, 20 cm×20 cm×2 mm, methanol:chloroform=1:20, v/v) to give the title compound (90 mg) as a colorless foam: 1H NMR (400 MHz, CDCl3) δ 1.44 (s, 9H), 1.45 (s, 9H), 1.69-1.84 (m, 5H), 1.90-2.03 (m, 1H), 2.09-2.28 (m, 3H), 2.68-2.83 (m, 3H). 3.39-3.46 (m, 1H), 3.50-3.56 (m, 1H), 3.74-3.81 (m, 1H), 3.93-3.99 (m, 1H), 4.01-4.08 (m, 1H), 4.29-4.37 (m, 1H), 4.45-4.53 (m, 2H), 4.57-4.76 (m, 2H), 4.91-4.98 (m, 1H), 7.15-7.30 (m, 5H), 7.38-7.53 (m, 2H), 7.63-7.70 (m, 1H), 7.81-7.87 (m, 1H), 8.57-8.60 (m, 1H), 8.66-8.70 (br s, 1H), and 9.93 (br s, 1H).

Workup

  1. customevaporated 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. customevaporated in vacuo
  6. customThe residue was purified by preparative thin layer chromatography (Whatman, PLK5F Silica Gel 50, 20 cm×20 cm×2 mm, methanol

Sources & evidence

ORD record
ord-977bbe00e11e4c759c4a99352538280c
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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