Synthesis of 3-substituted-4(3H)-quinazolinones via HATU-mediated coupling of 4-hydroxyquinazolines with amines

Organic Letters

Volumn 11, Issue 6, 2009, Pages 1421-1424

  Xiao, Zili ^a   Yang, Michael G ^a   Li, Peng ^a   Carter, Percy H ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE; QUINAZOLINONE DERIVATIVE;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; COMBINATORIAL CHEMISTRY; SYNTHESIS;

AMINES; COMBINATORIAL CHEMISTRY TECHNIQUES; MOLECULAR STRUCTURE; QUINAZOLINONES;

EID: 64049114368     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol802946p     Document Type: Article

References (28)

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17. Compound 7a was the only product observed under the following reaction conditions: in MeCN at rt with 3 equiv of 5a, 1.3 equiv of BOP, 1 equiv of 4a, and 1.5 equiv of DBU.
18. A closely related analogue of 4-hydroxyquinazolines was also studied, and the experimental result is described in the Supporting Information (see Note 2).
19. An abundance of starting material 4d remained even after heating for 20 h. See the Supporting Information (Note 3) for further description of the reaction yields.
20. To optimize reaction yield, the reaction of 4b with 5c (entry 2, Table 4) was heated at 50 °C for 16 h, but the yield was not improved.
21. The reaction was conducted at room temperature for 16 h with 20 equiv of tButyl amine and no desired product was observed by LC/MS analysis. The reaction mixture was then heated at 75 °C for 60 h. After work-up and chromatographic purification, the product 9d was isolated in 11% yield.
22. Amino phenylacetic acid was used for the reaction of 4-hydroxyquinazoline 4b under the reaction conditions of 75 °C for 16 h. No desired product was observed by LC/MS analysis except the remaining starting material.
23. 2O and EtOAc solution. The crystal structure analysis of 9f can be found in the Supporting Information section.
24. Detailed results are provided in the Supporting Information section (see Note 4).
25. A plausible explanation of this observation is discussed in the Supporting Information section (see Note 5).
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