4-Quinolinecarboxylic acid → 4-[(4-quinolinylcarbonyl)amino]-L-phenylalanine

HRID 1976962Notes

Reaction equation

HRID 1976962 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C@@H:7]([C:26]([OH:28])=[O:27])[NH:8]C(OCC2C3C=CC=CC=3C3C2=CC=CC=3)=O)=[CH:4][CH:3]=1.[N:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]([C:41](O)=[O:42])=[CH:33][CH:32]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1>[N:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]([C:41]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:6][C@@H:7]([C:26]([OH:28])=[O:27])[NH2:8])=[CH:29][CH:30]=2)=[O:42])=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 102434-Quinolinecarboxylic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 7019927Fmoc-4-Amino-L-phenylalanine2×

Product 1

HCID 537339864-[(4-quinolinylcarbonyl)amino]-L-phenylalanine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A 250 mL cylindrical glass vessel equipped with a coarse glass frit was charged with 4-amino-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-phenylalanine on Wang resin (10 g) obtained in Example 36 and a solution prepared from quinoline-4-carboxylic acid (5.2 g, 30 mmol), BOP (13.75 g, 30 mmol) and diisopropylethylamine (6.8 mL) in 70 mL of NMP. The slurry was agitated for 4 hours. The mixture was filtered and washed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL). To the washed resin was added a solution of 25% piperidine in NMP (80 mL), the mixture was agitated at room temperature for 20 minutes and filtered. The process was repeated and the resulting slurry was filtered and washed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL). Filtration afforded 4-[[(4-quinolinyl)carbonyl]amino]-L-phenylalanine on Wang resin suitable for use in the next step.

Workup

  1. customA 250 mL cylindrical glass vessel equipped with a coarse glass frit
  2. filtrationThe mixture was filtered
  3. washwashed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL)
  4. additionTo the washed resin was added a solution of 25% piperidine in NMP (80 mL)
  5. stirringthe mixture was agitated at room temperature for 20 minutes
  6. filtrationfiltered
  7. filtrationthe resulting slurry was filtered
  8. washwashed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL)
  9. filtrationFiltration

Sources & evidence

ORD record
ord-a3e9b73cf2874c33a8560e0a483ef808
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

Loading…