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

HRID 1282607Notes

Reaction equation

HRID 1282607 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>CN1CCCC1=O>[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-phenylalanine

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 (10 g) obtained in Example 62 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 N-methylpyrrolidinone. The slurry was agitated for 4 hr. 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 N-methylpyrrolidinone (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-quinolinylcarbonyl)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 N-methylpyrrolidinone (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-c524403393c3485a970fc97faf554bcb
Source dataset
uspto-grants-2002_09
Patent number
US06455550B1

Reaction notes

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