Oxalyl chloride → 4-[[(2,4-Dimethylpyridin-3-yl)Carbonyl]Amino]-N-[[1-[4-(methylsulfonyl)Butyl]Cyclopentyl]Carbonyl]-L-Phenylalanine

HRID 393474Notes

Reaction equation

HRID 393474 reaction equation
C[C:2]1([C:9](O)=O)[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][NH:3]1.C(Cl)(=O)[C:13](Cl)=[O:14].C[O:19][C:20](=[O:46])[C@H:21]([CH2:38][C:39]1[CH:44]=[CH:43][C:42]([NH2:45])=[CH:41][CH:40]=1)[NH:22][C:23]([C:25]1([CH2:30][CH2:31][CH2:32][CH2:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:24].CCN(C(C)C)C(C)C>ClCCl.O.CN(C=O)C>[CH3:9][C:2]1[C:7]([C:13]([NH:45][C:42]2[CH:41]=[CH:40][C:39]([CH2:38][C@@H:21]([C:20]([OH:19])=[O:46])[NH:22][C:23]([C:25]3([CH2:30][CH2:31][CH2:32][CH2:33][S:34]([CH3:37])(=[O:35])=[O:36])[CH2:26][CH2:27][CH2:28][CH2:29]3)=[O:24])=[CH:44][CH:43]=2)=[O:14])=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 542143104-amino-N-[[1-[4-(methylsulfonyl)butyl]cyclopentyl]carbonyl]-L-phenylalanine methyl esterHCID 698447482,4-Dimethylpyridinecarboxylic acid

Product 1

HCID 112727284-[[(2,4-Dimethylpyridin-3-yl)Carbonyl]Amino]-N-[[1-[4-(methylsulfonyl)Butyl]Cyclopentyl]Carbonyl]-L-PhenylalanineYield 85.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 2,4-dimethylpyridinecarboxylic acid (0.6 mmol, 102 mg) in dichloromethane (3 mL) was added a drop of DMF and oxalyl chloride (0.78 mmol, 99 mg) at 0° C. (ice bath). The solution was stirred at this temperature for 30 min, warmed to room temperature and stirred for an additional 1 h. Then, the solvent and excess oxalyl chloride was removed under vacuum and the residue was dried under high vacuum. To this 4-amino-N-[[1-[4-(methylsulfonyl)butyl]cyclopentyl]carbonyl]-L-phenylalanine methyl ester (0.5 mmol, 212 mg) was added and the mixture was dissolved in dichloromethane (5 mL). To this clear solution was added DIPEA (2.0 mmol, 0.258 g) at room temperature. The mixture was stirred for 15 h at which time TLC analysis of the mixture indicated the absence of starting material. Then, the mixture was diluted with dichloromethane (20 mL) and water (100 mL). The two layers were separated and the organic layer was washed with saturated sodium bicarbonate solution (20 mL), brine solution (30 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent gave a crude product which was purified by silica gel column chromatography to afford 0.232 g (80%) of a white solid. HR MS (C29H39N3O6S): Obs. mass, 558.2629. Calcd. mass, 558.2638, M+H).

Workup

  1. stirringstirred for an additional 1 h
  2. customThen, the solvent and excess oxalyl chloride was removed under vacuum
  3. customthe residue was dried under high vacuum
  4. stirringThe mixture was stirred for 15 h at which time TLC analysis of the mixture
  5. customThe two layers were separated
  6. washthe organic layer was washed with saturated sodium bicarbonate solution (20 mL), brine solution (30 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationFiltration of the drying agent and removal of the solvent
  9. customgave a crude product which
  10. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-fed86d3bec5e495cb1f257bc35a1d05d
Source dataset
uspto-grants-2004_10
Patent number
US06806365B2

Reaction notes

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