Solid phase synthesis of tetrahydro-1,4-benzodiazepin-2-ones

Tetrahedron Letters

Volumn 44, Issue 46, 2003, Pages 8493-8495

  Hone, Neal D ^a   Wilson, William ^a   Reader, John C ^a  

^a Millennium Pharmaceuticals Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BENZODIAZEPIN 2 ONE DERIVATIVE;

ALKYLATION; AQUEOUS SOLUTION; ARTICLE; DERIVATIZATION; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; REACTION ANALYSIS; STRUCTURE ANALYSIS; TECHNIQUE;

EID: 0141956487     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2003.09.108     Document Type: Article

References (11)

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2. Breslin H.J., Kukla M.J., Kromis T., Cullis H., De Knaep F., Pauwels R., Andries K., De Clercq E., Janssen M.A.C., Janssen P.A.J. Bioorg. Med. Chem. 7:1999;2427-2436.
3. Nakagawa, T.; Tokumasu, M.; Tashiro, M.; Takahashi, M.; Kayahara, T.; Takehana, S.; Kajigaya, Y.; Yoshida, K.; Sakurai, K. Pat. WO 0226732 A1 20020404.
4. Bhalay G., Blaney P., Palmer V.H., Baxter A.D. Tetrahedron Lett. 38:1997;8375-8378.
5. Wu Z., Ercole F., FitzGerald M., Perera S., Riley P., Cambell R., Pham Y., Rea P., Sandanayake S., Mathieu M.N., Bray A.M., Ede N.J. J. Comb. Chem. 5:2003;166-171.
6. Novabiochem 1.3 mmol/g 1% DVB polystyrene.
7. Alkyl halides used were methyl iodide, bromoacetamide, benzyl bromide, 3-methoxybenzyl bromide, 4-chlorobenzyl bromide and 4-cyanobenzyl bromide. The unalkylated amide 8 was also taken through steps iv-vi.
8. Electrophiles used were acetic anhydride, cyclohexanecarbonyl chloride, 3-cyclopentylpropionyl chloride, benzoyl chloride, 4-chlorobenzoyl chloride, 2-fluorobenzoyl chloride, 2-cyanobenzenesulphonyl chloride, 4-cyanobenzoyl chloride, 4-methoxybenzoyl chloride, 2-furoyl chloride, isoxazole-5-carbonyl chloride, 4-methoxybenzenesulphonyl chloride, benzenesulphonyl chloride, 4-chlorobenzenesulphonyl chloride, 3,5-difluorobenzenesulphonyl chloride, ethyl isocyanate, cyclopentyl isocyanate, allyl isocyanate, ethyl chloroformate, benzyl isocyanate, benzyl bromide, 4-chlorobenzyl bromide and 3-methoxybenzyl bromide. The underivatised amine was also taken through step vi.
9. Amines used were ammonia, n-propylamine, N,N-dimethylethylenediamine, ethanolamine, pyrrolidine, morpholine, 2-methoxyethylamine and benzylamine.
10. +).
11. 4OAc in water. The gradient was 5% B, 0-3 min; 5-100% B, 3-25 min; 100% B, 25-27 min; 100-5% B, 27-27.5 min.