Preparation and novel reduction reactions of vinamidinium salts.
Substituted acetic acids and formamides react in the presence of phosphorus oxychloride to yield the vinamidinium hexafluorophosphate salts 5a-d, 6a-d, and 7 in moderate to good unoptimized recrystallized yields (40-67%) as easily handled nonhygroscopic solids. The 1,3-differentially substituted vinamidinium salts 8 was prepared by amine exchange in 81% yield as are the cyclic diazapinium salts 9 and 10 in > 76% yield. The symmetrical 2-chlorovinamidinium 11 was prepared by displacement of 3 in 71% yield. The 2-chlorovinamidinium salts are cleanly reduced to the parent vinamidinium salts 12-16 using HI or PPh3/pTSA in up to 99% assay yield.
Davies
I W
IW
Department of Process Research, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. ian_davies1@merck.com
Taylor
M
M
Marcoux
J F
JF
Wu
J
J
Dormer
P G
PG
Hughes
D
D
Reider
P J
PJ
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D000077613:Etoricoxib; D007202:Indicators and Reagents; D007527:Isoenzymes; D010084:Oxidation-Reduction; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007202:Indicators and Reagents; D007527:Isoenzymes; D010880:Piperidines; D011725:Pyridines; D013450:Sulfones; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000077613:Etoricoxib