Two New Syntheses of a 4-Aminopyrazole: Condensation of an N-Substituted Vinamidinium Salt with a Functionalized Hydrazine

Abstract

Two novel syntheses of a key 4-aminopyrazole synthetic building block are described. Both routes avoid the potentially explosive precursors that were used in the previously patented route. A salt of a vinamidinium cation previously used in 5-aminopyrimidine synthesis was condensed with a protected hydrazine salt leading to a 4-aminopyrazole. Buchwald-type amination coupling has also been shown to yield the same compound.

Key words

heterocycles - pyrazoles - condensation - vinamidinium - Buchwald coupling

References

• 1 Heron NM, Pasquet GR, Mortlock AA, and Jung FH. inventors; WO Patent  WO2004094410.  ; Chem. Abstr. 2004, 141, 395569
• 2 Foote KM. inventors; WO Patent  WO2006129064.  ; Chem. Abstr. 2006, 146, 45534
• 3 Hüttel R. Büchele F. Chem. Ber.  1955,  88:  1586 
• 4 Nishiwaki N. Ogihara T. Takami T. Tamura M. Ariga M. J. Org. Chem.  2004,  69:  8382 
• 5 Alberti C. Tironi C. Bainotti F. Deleide G. Farmaco  1977,  32:  92 
• 6a Adams F. Gompper R. Kujath E. Angew. Chem., Int. Ed. Engl.  1989,  28:  1060 ; Angew. Chem. 1989, 101: 1043
• 6b Gupton JT. Hicks FA. Smith SQ. Main AD. Petrich SA. Wilkinson DR. Sikorski JA. Katritzky AR. Tetrahedron  1993,  49:  10205 
• 7 Valiullin VA. Ivakhnenko TE. Ivakhnenko EP. Doklady Chem.  2004,  399:  214 
• 8 Ragan JA. McDermott RE. Jones BP. am Ende DJ. Clifford PJ. McHardy SJ. Heck SD. Liras S. Segelstein BE. Synlett  2000,  1172 
• 9a Dousson CB. Heron NM. Hill GB. Synthesis  2005,  1817 
• 9b

  Note: the dihexafluorophosphate salt 8 (used to prepare 6) is now supplied commercially by Acros and Kanto under the name of ‘aminoreductone precursor’. The commercial product is listed as a tautomer of 8, but matches in its condensation chemistry that of the material previously described by us (Paul Warwick, personal communication)

• 10 Denni-Dischert D. Marterer W. Bänziger M. Yusuff N. Batt D. Ramsey T. Geng P. Michael W. Wang R.-MB. Taplin F. Versace R. Cesarz D. Perez LB. Org. Process Res. Dev.  2006,  10:  70 
• 11 Hill GB. inventors; WO Patent  WO2007034183.  ; Chem. Abstr. 2007, 350598