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

HRID 2185422Notes

Reaction equation

HRID 2185422 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:44])[CH2:40][N:41]([CH3:43])[CH3:42])[CH2:35][C@H:31]1[C:32]([OH:34])=O)=[O:29])([CH3:26])([CH3:25])[CH3:24].[N:45]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=[C:47]([NH:55][C:56](=[O:75])[C@@H:57]2[CH2:61][C@@H:60]([NH:62][C:63](=[O:74])[C@H:64]([OH:73])[CH2:65][CH2:66][C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=3)[CH2:59][NH:58]2)[CH:46]=1>ClCCl.C(N(CC)CC)C>[N:45]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=[C:47]([NH:55][C:56](=[O:75])[C@@H:57]2[CH2:61][C@@H:60]([NH:62][C:63](=[O:74])[C@H:64]([OH:73])[CH2:65][CH2:66][C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=3)[CH2:59][N:58]2[C:32](=[O:34])[C@@H:31]2[CH2:35][C@@H:36]([NH:38][C:39](=[O:44])[CH2:40][N:41]([CH3:43])[CH3:42])[CH2:37][N:30]2[C:28]([O:27][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:29])[CH:46]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341539N-tert-Butoxycarbonyl-trans-4-(N,N-Dimethylglycylamino)-L-ProlineHCID 59895122trans-4-((R)-2-Hydroxy-4-Phenylbutrylamino)-L-Proline 3-Quinolylamide

Product 1

HCID 21341541N-tert-Butoxycarbonyl-trans-4-(N,N-Dimethylglycyl)amino-L-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-Proline 3-Quinolylamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (33 μL), 1-hydroxybenzotriazole (30 mg), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (46 mg) were added to a suspension of the crude N-tert-butoxycarbonyl-trans-4-(N,N-dimethylglycylamino)-L-proline (B) and trans-4-((R)-2-hydroxy-4-phenylbutyrylamino)-L-proline 3-quinolylamide (Compound D101 (H), 84 mg) in dichloromethane (5 mL) at 0° C. After stirring at 0° C. for 30 min and at room temperature for 14 hr, the solvent was removed in vacuo. The residue was diluted with saturated sodium hydrogen carbonate and extracted with chloroform-methanol (10:1,v/v). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was purified by preparative thin layer chromatography (Whatman, PLK5F Silica Gel 150, chloroform:methanol=10:1, v/v) to afford the title compound (76 mg) as a colorless glassy solid: mass spectrum (EI+) m/e 715 (M+); (FAB+) m/e 716 (M+1).

Workup

  1. customthe solvent was removed in vacuo
  2. additionThe residue was diluted with saturated sodium hydrogen carbonate
  3. extractionextracted with chloroform-methanol (10:1,v/v)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by preparative thin layer chromatography (Whatman, PLK5F Silica Gel 150, chloroform

Sources & evidence

ORD record
ord-4370e04f32e54440a5e7e9f314e341e7
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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