4-Quinolinecarboxylic acid → HCID 11191627, compound

HRID 1282594Notes

Reaction equation

HRID 1282594 reaction equation
C[O:2][C:3](=[O:28])[C@H:4]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=1)[NH:5][C:6]([C:8]1([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7].[N:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]([C:39]([OH:41])=O)=[CH:31][CH:30]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[OH-].[Na+]>CN(C=O)C.C(OCC)(=O)C.CCOCC.CO>[C:14]1([CH2:13][C:8]2([C:6]([NH:5][C@H:4]([C:3]([OH:28])=[O:2])[CH2:20][C:21]3[CH:22]=[CH:23][C:24]([NH:27][C:39]([C:32]4[C:33]5[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=5)[N:29]=[CH:30][CH:31]=4)=[O:41])=[CH:25][CH:26]=3)=[O:7])[CH2:12][CH2:11][CH2:10][CH2:9]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

10

Reactant 5

HCID 102434-Quinolinecarboxylic acidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 538418674-amino-N-[[1-(phenylmethyl)cyclopentyl]carbonyl]-L-phenylalanine methyl ester

Product 1

HCID 11191627HCID 11191627, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-amino-N-[[1-(phenylmethyl)cyclopentyl]carbonyl]-L-phenylalanine methyl ester (29.5 mg, 0.078 mmol), quinoline-4-carboxylic acid (17 mg, 0.10 mmol), and HBTU (38 mg, 0.10 mmol) in 1 mL of DMF was treated with diisopropylethylamine (30 μL, 0.17 mmol). The mixture was stirred over night and was diluted with 15 mL of ethyl acetate and 10 mL of ether and was washed with portions of water (2×10 mL), saturated NaHCO3 (10 mL) and was dried (MgSO4). Concentration gave 48 mg which was dissolved in 3 mL of methanol. Sodium hydroxide solution (0.10 mL, 4 N, 0.4 mmol) was added and the mixture was stirred for 2 hr. The excess base was quenched by addition of 0.1 mL of acetic acid, the solution was filtered through a 0.2μ nylon filter and the filtrate was purified by RP-HPLC on a 4×30 cm Rainin C-18 column using a gradient of 5 to 95% acetonitrile:water containing 0.75% trifluoroacetic acid at a flow of 49 mL/min over 30 min. The peak eluting at 74.5% acetonitrile was the acid N-[[1-(phenylmethyl)cyclopentyl]carbonyl-4-[(4-quinolinylcarbonyl)amino)-L-phenylalanine (15 mg), HR-FAB-MS: obs. mass 522.2393. Calcd. mass 522.2393 (M+H), the peak eluting at 83% acetonitrile was recovered N-[[1-(phenylmethyl)cyclopentyl]carbonyl]-4-[(4-quinolinylcarbonyl)amino]-L-phenylalanine methyl ester (15 mg), HR-FAB-MS: obs. mass 536.2556. Calcd. mass 536.2549 (M+H).

Workup

  1. washwas washed with portions of water (2×10 mL), saturated NaHCO3 (10 mL)
  2. dry with materialwas dried (MgSO4)
  3. concentrationConcentration
  4. customgave 48 mg which
  5. stirringthe mixture was stirred for 2 hr
  6. customThe excess base was quenched by addition of 0.1 mL of acetic acid
  7. filtrationthe solution was filtered through a 0.2μ nylon
  8. filtrationfilter
  9. customthe filtrate was purified by RP-HPLC on a 4×30 cm Rainin C-18 column
  10. washThe peak eluting at 74.5% acetonitrile
  11. washmass 522.2393 (M+H), the peak eluting at 83% acetonitrile
  12. customwas recovered N-[[1-(phenylmethyl)cyclopentyl]carbonyl]-4-[(4-quinolinylcarbonyl)amino]-L-phenylalanine methyl ester (15 mg), HR-FAB-MS

Sources & evidence

ORD record
ord-f78aa3100212489e93b14107e0951e7f
Source dataset
uspto-grants-2002_09
Patent number
US06455550B1

Reaction notes

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