The Preparation and Properties of some Pyrazolo/1, 5-c/Pyramidines and Pyrazolo/1, 5-c/quinazolines

  • Peter R. Morris

Student thesis: Doctoral ThesisDoctor of Philosophy


Four types of pyrazolopyrimidines can theoretically exist. Pyrazolo
|3,4-d| pyrimidines and pyrazolo|4, 3-d|pyrimidines do not contain a
bridgehead nitrogen atom, and their syntheses and properties are reported
elsewhere. Pyrazolo||,5-alpyrimidines and pyrazolo|1,5-c|pyrimidines
contain a nitrogen atom, common to both the pyrazole and pyrimidine rings.
The syntheses and properties of pyrazolo|1,5-al|pyrimidines are comprehensively
reviewed here. Pyrazoto|1,5-c|pyrimidines were, at the commencement of
this work, unreported in the literature (the ring index refers to this
heterocycle, but the subject of the reference therein is a pyrazolo||,5-a|
pyrimidine ) but in 1972 a synthesis of this ring system was reported and
some electrophilic substitution reactions were mentioned. These are
reported in the introduction.

The preparations of pyrazolo||,5-a|quinazolines and pyrazolo|1,5-c|
quinazolines, the tricyclic analogues of the fused pyrimidines mentioned
above, are reviewed here, partly because of their similarity to the
pyrazolopyrimidines structurally, but also because of the biological
activities (psychomotor depression and antibacterial activity) reported
for the|1,5-c¦series.

Many references to the preparation and properties of pyrazolo|1,5-a|
pyrimidines mention biological activity; antiimflammatory, analgesic,
anti-tumour activities are reported. Derivatives of pyrazoles from which
these compounds are synthesised have for many years been recognised to
possess anti-inflammatory activity but anti-tumour properties have also
been attributed to some derivatives: which include the fused pyrazolo|3,4-d|
pyrimidines 124 Pyrazolo|4,3-d|pyrimidines also possess biological activity
and their syntheses are reported elsewhere.

It seemed desirable then to inovate the synthesis of pyrazolo|1,5-c|
pyrimidines for two reasons; a) this heterocycle was unreported in the
literature b) since other pyrazolopyrimidines possess biological activity,
the possibility of activity in the pyrazolo|1,5-clpyrimidines should be
investigated. (Biological reports have not yet been received).

The great activity of the C- and N- glycosides of many heterocyclic
compounds suggests that the ribosylation of pyrazolo|1,5-c|pyrimidines
and pyrazolo|1,5-c|quinazol ines might produce compounds of greater potency,
and therefore, the activity of these heterocycles to electrophilic reagents
was investigated experimentally.

A successful route to pyrazolo|1,5-c|pyrimidines from S5-Tormy |-5—
methy lpyrazole was obtained. A route from 4-methylpyrimidines was less
successful. 2-methy Ipyrazolo|1,5-c|quinazoline was prepared essentially
by methods reported in the literature and the novel 2-hydroxy derivative
was obtained by a similar procedure.

Electrophilic substitution was possible only with the stronger
electrophiles (No2, Br2, +CHO). 2-Hydroxy pyrazolo|1,5-c|quinazoline
appeared to be less reactive to electrophiles than the 2-methy! derivative,
and was less stable in dilute acid. Ring cleavage occurred over a period
of thirty minutes.
Date of Award1973
Original languageEnglish


  • preparation
  • properties
  • pyrazolo/1
  • 5-c/pyramidines
  • 5-c/quinazo-lines

Cite this