Solid phase synthesis of 1,6-disubstituted 2,3-diketopiperazines and 1,2-disubstituted piperazines from N-acylated amino acids

Tetrahedron Letters

Volumn 40, Issue 49, 1999, Pages 8539-8542

  Nefzi, Adel ^a   Giulianotti, Marc A ^a   Houghten, Richard A ^a  

^a TORREY PINES INSTITUTE FOR MOLECULAR STUDIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,3 DIKETOPIPERAZINE DERIVATIVE; AMINO ACID; BENZOTRIAZOLE DERIVATIVE; CARBOXYLIC ACID; CYANAMIDE; IMIDAZOLE DERIVATIVE; N ACYLAMINO ACID; PIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG PURIFICATION; PARTIAL DRUG SYNTHESIS; SOLID;

EID: 0033521165     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01823-7     Document Type: Article

References (23)

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16. 3-THF (40x). The tubes were heated at 65°C for 72 h, followed by quenching with MeOH. The resin was then washed with methanol (4x) and the borane disproportionated by treatment with piperidine at 65°C overnight. The resin was then washed with DMF (6x) and methanol (2x) and dried. (3) Disubstituted diketopiperazine formation: The cyclization occurred following treatment of the resin-bound reduced N-acylated amino acid overnight with fivefold excess of oxalyldiimidazole (0.1 M) in anhydrous DMF. Following cleavage from the resin with anhydrous HF in the presence of anisole at 0°C for 90 min, the desired product was extracted with acetonitrile:water (50:50) and lyophilized. (4) Piperazine formation: The resin-bound diketopiperazine was treated in the same conditions described above for the reduction of the amide bonds. Following cleavage from the resin with anhydrous HF in the presence of anisole at 0°C for 7 h, the desired product was extracted with acetonitrile:water (50:50) and lyophilized.
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