A facile one-pot preparation of alkyl aminoaryl sulfides for the synthesis of GW7647 as an agonist of peroxisome proliferator-activated receptor alpha.
We have developed two simple and high yielding one-pot syntheses of alkyl aminoaryl sulfides containing a series of four-steps: in situ protection of the free amine by reaction with a Grignard reagent, halogen-lithium exchange, sulfur insertion, and a substitution reaction with various electrophiles. Through this protocol, we have successfully synthesized tert-butyl-2-[4-(2-aminoethyl)phenylsulfanyl]-2-methylpropanoate, a key intermediate for the synthesis of GW7647 and GW9578 (ureido-TiBAs), in 92% yield. Furthermore, we were able to improve the overall yield of GW7647 to 66%, 3 times the yield previously reported.
Ham
Jungyeob
J
Center for Marine Natural Products and Drug Discovery, School of Earth and Environmental Sciences, Seoul National University, NS-80, Seoul 151-747, Korea.
Cho
Sung Jin
SJ
Ko
Jaeyoung
J
Chin
Jungwook
J
Kang
Heonjoong
H
D000588:Amines / Q000737:chemistry; D002087:Butyrates / Q000138:chemical synthesis* / Q000494:pharmacology; D006219:Halogens / Q000737:chemistry; D008094:Lithium / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists*; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry
D000588:Amines; D002087:Butyrates; C453899:GW 7647; D006219:Halogens; D047493:PPAR alpha; D010671:Phenylurea Compounds; D013440:Sulfides; D008094:Lithium; C121804:GW 9578; D008274:Magnesium