2,6-Dimethylbenzoic acid → N-[(2,6-dimethylphenyl)carbonyl]-4-[[(4-quinolinyl)carbonyl]amino]-L-phenylalanine

HRID 1976963Notes

Reaction equation

HRID 1976963 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]([NH:13][C:14]2[CH:25]=[CH:24][C:17]([CH2:18][C@@H:19]([C:21]([OH:23])=[O:22])[NH2:20])=[CH:16][CH:15]=2)=[O:12])=[CH:3][CH:2]=1.[CH3:26][C:27]1[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[C:28]=1[C:29](O)=[O:30].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>ClCCl.CO.CN(C)C=O.CN1CCCC1=O>[CH3:26][C:27]1[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[C:28]=1[C:29]([NH:20][C@H:19]([C:21]([OH:23])=[O:22])[CH2:18][C:17]1[CH:24]=[CH:25][C:14]([NH:13][C:11]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:1]=[CH:2][CH:3]=2)=[O:12])=[CH:15][CH:16]=1)=[O:30]

Participants

9

Reactant 4

HCID 124392,6-Dimethylbenzoic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 537339864-[(4-quinolinylcarbonyl)amino]-L-phenylalanine

Product 1

HCID 44291330N-[(2,6-dimethylphenyl)carbonyl]-4-[[(4-quinolinyl)carbonyl]amino]-L-phenylalanine

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-[[(4-Quinolinyl)carbonyl]amino]-L-phenylalanine on Wang resin (300 mg, 0.20 mmol) was washed with dichloromethane (2×10 mL), methanol (2×10 mL) and dimethylformamide (2×10 mL). To the resin was added a solution prepared from 2,6-dimethylbenzoic acid (150 mg, 1.0 mmol), BOP (450 mg, 1.02 mmol) and diisopropylethylamine (0.23 mL) in 4 mL of N-methylpyrrolidone at room temperature. The resulting mixture was agitated for 2 hr. The reaction mixture was then filtered and washed with dichloromethane (2×10 mL), methanol (2×10 mL) and dichloromethane (2×10 mL). Cleavage was effected by treatment with 90% trifluoroacetic acid (TFA) in dichloromethane for 5 minutes. The mixture was filtered and the TFA was removed under high vaccum. Addition of ether (25 mL) effected precipitation of N-[(2,6-dimethylphenyl)carbonyl]-4-[[(4-quinolinyl)carbonyl)amino]-L-phenylalanine (0.16 g).

Workup

  1. additionTo the resin was added a solution
  2. filtrationThe reaction mixture was then filtered
  3. washwashed with dichloromethane (2×10 mL), methanol (2×10 mL) and dichloromethane (2×10 mL)
  4. waitCleavage was effected by treatment with 90% trifluoroacetic acid (TFA) in dichloromethane for 5 minutes
  5. filtrationThe mixture was filtered
  6. customthe TFA was removed under high vaccum
  7. additionAddition of ether (25 mL)
  8. customprecipitation of N-[(2,6-dimethylphenyl)carbonyl]-4-[[(4-quinolinyl)carbonyl)amino]-L-phenylalanine (0.16 g)

Sources & evidence

ORD record
ord-7bc7c8887d0e4c5b927b4528725b12ad
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

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