A novel solid-phase synthesis of di- and trisubstituted N-acyl ureas

Tetrahedron Letters

Volumn 44, Issue 36, 2003, Pages 6931-6935

  Ravn, Jacob ^a   Ankersen, Michael ^a   Begtrup, Mikael ^b   Lau, Jesper F ^a  

^a NOVO NORDISK A S   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CARBOXYLIC ACID; RESIN; UREA DERIVATIVE;

ACIDIFICATION; ADDITION REACTION; ARTICLE; REACTION ANALYSIS; SOLID STATE; SUBSTITUTION REACTION;

EID: 0041657861     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)01676-9     Document Type: Article

References (17)

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12. Alternatively, the N-benzoyl urea might be the result of acylation of the urea with benzoic anhydride generated concomitantly. However, no such acylation was observed after overnight treatment of a resin bound trisubstituted urea with benzoic anhydride and triethylamine.
13. Wang polystyrene resin (100-200 mesh, 1% DVB, 1.07 mmol/g) was purchased form BACHEM, Switzerland.
14. General procedure: Resin 9 was synthesized by the same procedure as reported in Ref. 6. All washings were performed with 5 mL of solvent. To a solution of hexachloroethane (404 mg, 1.71 mmol) in dry THF (5 mL) was added triphenylphosphine (448 mg, 1.71 mmol) and the mixture was stirred for 30 min and then added to resin 9 (300 mg, 0.171 mmol) preswelled in dry THF. The resin was shaken for 5 h and then filtered and washed with dry THF (5×). A solution of benzoic acid (209 mg, 1.71 mmol) and triethylamine (0.33 mL, 1.71 mmol) in dry 1,4-dioxane (5 mL) was added and the mixture shaken for 16 h. After filtration, the resin was washed with DCM (3×), DCM/MeOH (3×), AcOH/MeOH/THF 1:2:7 (1×) and DCM (5×) and the product was cleaved from the support by treatment with TFA/DCM 1:1 for 1 h. The solvents were evaporated under reduced pressure and the residue was dissolved in acetonitrile. A small portion was removed for concentration studies and LC-MS and the remainder was purified by preparative HPLC.
15. 6) δ 23.5, 25.0, 40.7, 49.0, 127.8, 128.6, 128.7, 129.8, 131.8, 134.7, 135.4, 135.6, 155.9, 158.4, 173.0.
16. Khorana H.G. J. Chem. Soc. 1952;2081-2088.
17. 6) δ 42.5, 44.6, 126.82, 126.2, 126.7, 126.8, 127.3, 127.7, 128.2, 129.5, 132.6, 134.9, 135.8, 138.3, 153.9, 157.1, 157.5.