Asymmetric synthesis of the carbon-14-labeled selective glucocorticoid receptor modulator using cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate.
We describe in this study the asymmetric synthesis of radioisotope (RI)-labeled selective glucocorticoid receptor modulator. This synthesis is based on optimization of the cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate and Negishi coupling of zinc cyanide to the 6-bromoindole moiety. [¹⁴C] Labeled (-)-{4-[(1-{2-[6-cyano-1-(cyclohexylmethyl)-1H-indol-3-yl]-3,3,3-trifluoro-2-hydroxypropyl}piperidin-4-yl)oxy]-3-methoxyphenyl}acetic acid (-)-1 was synthesized successfully with high enantioselectivity (>99% ee) and sufficient radiochemical purity.
Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd., 33-94 Enoki, Suita, Osaka 564-0053, Japan.
Takaaki
T
Sumiyoshi
Daisuke
D
Urabe
Kengo
K
Tojo
Masato
M
Sakamoto
Kazumi
K
Niidome
Norie
N
Tsuboya
Tomoko
T
Nakajima
Masanori
M
Tobe
D002250:Carbon Radioisotopes; D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D019289:Pyruvic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D013696:Temperature
C575317:(4-((1-(2-(6-cyano-1-(cyclohexylmethyl)-1H-indol-3-yl)-3,3,3-trifluoro-2-hydroxypropyl)piperidin-4-yl)oxy)-3-methoxyphenyl)acetic acid; C575316:6-bromoindole; D002250:Carbon Radioisotopes; D002930:Cinchona Alkaloids; D007211:Indoles; D010880:Piperidines; D011965:Receptors, Glucocorticoid; C513102:ethyl trifluoropyruvate; D019289:Pyruvic Acid