Iodine chloride → 2-Amino-5-iodobenzonitrile

One general synthetic procedure for the methods of the present invention is depicted in Scheme 2 below. lodination of 2-aminobenzonitrile with iodine monochloride in glacial acetic acid (AcOH) at room temperature occurred regioselectively at the position para to the amino group to give 2-amino-5-iodobenzonitrile (9) in 65% yield as reported by others (Harris, N. V.; Smith, C.; Bowden, K. Eur. J. Med Chem. 1992; 27, 7-18). A catalytic amount (0.1 mmol) of commercially available [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II)′CH2Cl2 [(dppf)PdCl2—CH2Cl2] (Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.; Hirotsu, K. J. Am Chem. Soc. 1984, 106, 158-163) was added to a THF solution of the organozinc halide (5 mmol) resulting in the formation of a solution having a deep yellow color after a few minutes. After complete addition of (dppf)PdCl2 to the reaction mixture, a solution of aryl halide 9 (2 mmol) in THF was added to the reaction mixture and the mixture was then heated at reflux for 30 min. The cross-coupling reaction was complete by thin layer chromatography (TLC). The intermediate amino nitrile 10 formed by the cross-coupling reaction were purified by column chromatography on silica gel, and their identity and purity were established from their 1H NMR spectra, which contained the expected singlet at approximately δ 3.8, along with OMe, NH2, and aromatic proton peaks consistent with assigned structures (data provided below).

1. customat room temperature

ORD record

ord-6a70f3c578844d3fab3fb1ecec4972f5

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07256197B2