Download (6Mb) - Etheses - Saurashtra University

Chapter 4
Synthesis of highly substituted pyrazolopyrimidine
Synthesis of 5-amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-4-
carboxamide (5).
A 100mL conical flask equipped with magnetic stirrer and septum was
charged 2-cyano-N-cyclohexyl-3,3-bis(methylthio)acrylamide (4) (0.1mol) in
isopropyl alcohol (100 mL) and hydrazine hydrate (0.1mol). The Reaction mixture
was heated to reflux for 2 h. After completion of the reaction, it was poured into
50mL cold water. The precipitated crude product was purified by filtration followed
by crystallization from EtOH.
General synthesis of Acetoacetanilide derivatives (AAA) (8a-x).
A mixture containing the primary amine (7a-h) (10 mmol), β-keto esters (6ac)
(10 mmol), and catalytic amount of sodium or potassium hydroxide (10 %) in
toluene (50 mL) was refluxed at 110 o C for 12-15 h. The reaction was monitored by
TLC. After completion of reaction, the solvent was removed under vaccuo and the
residue was crystallized from methanol.
General synthesis of ketene dithioacetals (9a-x).
A 100mL conical flask equipped with magnetic stirrer and septum was
charged with a solution of acetoacetanilide derivatives (8a-x) (10 mmol) in DMF (10
mL). Dry K 2 CO 3 (20 mmol) was added and the mixture was stirred for 2 h at room
temperature. CS 2 (10 mmol) was then added and the mixture was stirred for an
additional 2 h at room temperature. Methyl iodide (20 mmol) was added at 0-5 o C and
the mixture was stirred for 4 h at room temperature. The reaction was monitored by
TLC. After completion, reaction mixture poured into water (50 mL). The precipitated
crude product was purified by filtration followed by crystallization from EtOH.
General synthesis of substituted and fused pyrazolopyrimidines (10a-x).
A mixture of 5-amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-4-
carboxamide (5) (3.0mmol), potassium carbonate (6.0mmol) and ketene dithioacetals
(9a-x) (3.0mmol) in isopropyl alcohol (10 mL) was heated to reflux for 7-10 h. The
progress of reaction mixture was monitored by TLC. After completion of reaction, the
mixture was cooled to room temperature and solid residue was filtered and washed
with 10mL of isopropyl alcohol followed by 50 ml of water. The product was
crystallized from MeOH to give 10a-x in 87-97% yield.
Department of Chemistry, Saurashtra university, Rajkot-360005 140