Two convenient regioselective syntheses of 1-N-alkyl-3-aryl-4-[pyrimidin-4-yl]-pyrazoles

Tetrahedron Letters

Volumn 50, Issue 13, 2009, Pages 1377-1380

  Ralph, Jeffrey M ^a   Faitg, Thomas H ^a   Silva, Domingos J ^a   Feng, Yanhong ^a   Blackledge, Charles W ^a   Adams, Jerry L ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PYRAZOLE DERIVATIVE;

ALKYLATION; ARTICLE; CHEMICAL REACTION; DRUG STRUCTURE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 59649118609     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2008.12.113     Document Type: Article

References (19)

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10. Interestingly, reaction of the 1-H-N-pyrazole with isocyanates or acyl chlorides afforded the beta isomer preferentially, in a 10:1 ratio or greater.
11. HPLC analysis of the crude reaction mixture showed a β-to-α ratio of 11:1.
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16. Compound 17 was also prepared from 9 in similar overall yield using a longer synthetic sequence based on the 4-iodo pyrazole intermediate shown below:{A figure is presented}.
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18. The enaminone was also prepared by reaction of the arylmethylketone with DMF-DMA as the solvent, but the yield was lower.
19. Guanidine 19 was prepared by treating 3-(4-methyl-piperazin-1-yl)-aniline with 1,3-bis(tert-butoxy-carbonyl)guanidine, followed by deprotection with 12 N HCl.