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Synthesis of isonipecotinoyl analogues of aminopterin and folic acid
Author(s) -
Sekikawa Isao,
Takahashi Yumiko
Publication year - 1983
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570200361
Subject(s) - chemistry , aminopterin , hydrolysis , guanidine , amino acid , glutamic acid , stereochemistry , acid hydrolysis , condensation , glutamate receptor , medicinal chemistry , methotrexate , organic chemistry , biochemistry , physics , immunology , biology , thermodynamics , receptor
The preparation of isonipecotinoyl analogues of aminopterin and methotrexate is described. Condensation of diethyl N ‐isonipecotinoyl‐L‐glutamate 4 with 2‐amino‐5‐bromomethyl‐3‐cyanopyrazine 5 afforded diethyl N ‐( N ‐[(2‐amino‐3‐cyanopyrazin‐5‐yl)methyl]isonipecotinoyl)‐L‐glutamate 6 . Cyclisation of 6 with guanidine followed by blocking group hydrolysis afforded N ‐([ N ‐(2,4‐diaminopteridin‐6‐yl)methyl]isonipecotinoyl)‐L‐glutamic acid 8 . Coupling of N ‐(2‐amino‐4(3 H )ioxopteridin‐6‐yl]methyl)isonipecotinic acid 11 with diethyl L‐glutamate gave diethyl N ‐[( N ‐[2‐amino‐4(3 H )‐oxopteridin‐6‐yl]methyl)isonipecotinoyl]‐L‐glutamate 12 . Blocking group hydrolysis afforded N ‐[( N ‐[2‐amino‐4(3 H )‐oxopteridin‐6‐yl]methyl)isonipecotinoyl]‐L‐glutamic acid 13 .