An improved and highly convergent synthesis of 4-substituted-pyrido[2,3-d]pyrimidin-7-ones

Tetrahedron Letters

Volumn 48, Issue 7, 2007, Pages 1205-1207

  Yan, Hongxing ^a   Boehm, Jeffrey C ^a   Jin, Qi ^a   Kasparec, Jiri ^a   Li, Huijie ^a   Zhu, Chongjie ^a   Widdowson, Katherine L ^a   Callahan, James F ^a   Wan, Zehong ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PYRIDO[2,3 D]PYRIMIDIN 7 ONE DERIVATIVE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION KINETICS; REACTION OPTIMIZATION; SUBSTITUTION REACTION; SYNTHESIS;

EID: 33846256288     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2006.12.064     Document Type: Article

References (14)

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7. Less than 5% of 3c was identified via LC-MS when treated under the condition of Ref. 2 (toluene, 200 °C, sealed tube). This is most likely due to the steric hinderance in the substrate.
8. Furukawa N., Ogawa S., Kawai T., and Oae S. Tetrahedron Lett. 24 (1983) 3243
9. This template is apparently more closely related to 4-chloro-2-methanesulfinyl-pyrimidine wherein chlorine exhibited selectivity over methanesulfinyl, see:. Hurst D.T., and Johnson M. Heterocycles 23 (1985) 611
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11. All boronic acids were purchased from commercial sources except 12h. For the preparation of 12h, see: Dack, K. N.; Whitlock, G. A. WO 99/29667, 1999.
12. 4 (0.02 equiv) was added. The reaction tube was sealed and irradiated with a microwave reactor at 150 °C for 15 min. The mixture was concentrated under vacuo. Flash chromatography (EtOAc/hexane) then provided compound 13.
13. As shown in Ref. 2, an oxidation reaction was carried out after the Suzuki cross-coupling and the group of -SMe would be likely oxidized in the reaction.
14. For Representative experimental procedures and compound characterization, see: Callahan, J. F.; Boehm, J.; Wan, Z.; Yan, H. WO 06/104917, 2006.