Preparation of polymer-bound pyrazolone active esters for combinatorial chemistry

Tetrahedron Letters

Volumn 44, Issue 44, 2003, Pages 8063-8067

  Byun, Jang Woong ^a   Lee, Dong Hoon ^a   Lee, Yoon Sik ^a  

^a Seoul National University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE; AMINE; ESTER DERIVATIVE; POLYMER; PYRAZOLONE; RESIN;

ACYLATION; ARTICLE; CHEMICAL MODIFICATION; CHEMICAL REACTION; COMBINATORIAL CHEMISTRY; HYDROLYSIS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY;

EID: 0141459403     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2003.09.044     Document Type: Article

References (32)

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27. 2/g) was swelled with DMF in a three-necked round-bottomed flask. The mixture of CNPO (11.4 g, 35.3 mmol), DIC (5.5 ml, 35.3 mmol) and DMAP (422.5 mg, 3.5 mmol) in DMF was then added and stirred for 24 h. The product resin was filtered and washed three times each with DMF, MeOH and DCM in turn, and then dried in a vacuum.
28. A general procedure for the coupling of the acyl chlorides to the polymer-bound CNPO linker (Resin III). Resin II (3.0 g, 1.01 mmol CNPO/g) was treated with benzoyl chloride (1.2 ml, 9.1 mmol) in 2% TEA/THF (v/v) and shaken for 2 h. The resin was washed three times each with DCM and MeOH, and dried under vacuum.
29. A general procedure for the coupling of the caboxylic acid derivatives to the polymer-bound CNPO linker (Resin III). Resin II (3.0 g, 1.01 mmol CNPO/g) was treated with a mixture of 4-nitrobenzoic acid (1.5 g, 9.1 mmol), DIC (1.6 ml, 10.0 mmol) and DMAP (36.7 mg, 0.9 mmol) in DMF and shaken for 24 h. The resin was washed three times each with DCM and MeOH, and then dried in vacuum.
30. -1) had completely disappeared.
31. A general procedure for the combinatorial synthesis of the amide derivatives. Benzoyl-CNPO-Resin III (0.3 g, 0.76 mmol/g) was swelled with DCM in a filtered vial. Piperidine (77.4 μl, 0.78 mmol) in THF (5 ml) was transferred into the reaction vessel and the reaction mixture was shaken for 1 h at room temperature. The resin was filtered and washed with DCM. The filtrate and the washing solution were combined and passed through a silica gel short column to remove the excess amine derivatives. After evaporating the solution, the amide product was obtained as a white solids (43.2 mg) and the yield was 99.7% based on the amount of the loaded benzoyl active ester groups.
32. 2O (90/10); 1.0 ml/min, 210 nm UV. The retention time of (S,R)-Boc-Phe-α-methylbenzylamide and (R,R)-Boc-Phe-α -methylbenzylamide were 13.7 and 13.2 min, respectively.