4-CHLORO-3-IODO-PYRIDIN-2-YLAMINE

A suspension of (4-chloro-3-iodo-pyridin-2-yl)-carbamic acid tert-butyl ester (5.6 g, 15.8 mmol) in 48percent hydrobromic acid was heated at 100° C. for 10 min to give a clear solution. The mixture was cooled, treated with crushed ice and made basic with 6 M NaOH. The precipitated product was collected by vacuum filtration, washed with HGeneral procedure: the previously synthetized compound (4.2 g, 11.86mmol) was dissolved into HBr 48percent (50 mL) and the solution was heated at 100°Cfor 10 minutes. The mixture was cooled at room temperature andwas poured with stirring into ice and water (100 mL). The resulting suspensionwas alkalinized with a 6M solution of NaOH (100 mL). The resulting solid wasfiltered, washed with water and dissolved into THF. The organic phase was driedover MgSOA solution of aqueous HBr (48percent, 10 mL, 13.26 mmol) was added to tert-butyl (4- chloro-3-iodopyridin-2-yl)carbamate (4.7 g, 13.26 mmol) and the suspension was stirred at RT for 3h. The reaction mixture was diluted with water (40 ml), basified with 2N NaOH and the resultant suspension was filtered, washed with water (4 x 1 mL) and dried to afford 4-chloro-3- iodopyridin-2-amine as white solid (3.05 g, 90percent yield). MS (ESI) m/z: 254.9 (M+HIntermediate 3 4-Chloro-3-iodopyridin-2-amine [0041] A 250 mL round bottom flask was charged with tert-butyl (4-chloro-3-iodopyridin-2-yl)carbamate (4.5 g, 12.69 mmol) and dissolved in DCE (50.8 mL). To that stirring solution was added anisole (2.77 mL, 25.4 mmol) followed by TFA (14.67 mL, 190 mmol) at rt. After 1.5 hours, LCMS showed clean and complete consumption of the starting material to a large peak with the desired mass (m/z=254[M+H]+Methanol/Water/TFA Phenomenex Luna C18, 30×2 mm, 3u ES+/−). The mixture was concentrated under reduced pressure into a collection bulb that was pretreated with 3.0 M NaOH. The crude mixture was then redissolved in toluene to aid in the removal of any volatiles. The crude solid was then diluted with EtOAc and sat'd sodium bicarbonate. The mixture was stirred for 15 min. The contents of the flask were transferred into a separatory funnel where the aqueous layer was extracted twice with EtOAc and discarded. The combined organics were washed with brine, dried with magnesium sulfate, and concentrated under reduced pressure. The crude material was dissolved in a small amount of ethanol and then heated with a heat gun. The mixture was let sit and then after 5 min cooled in an acetone dry ice bath. The solids were sonicated and collected by filtration. The mother liquor was concentrated and the above procedure was repeated. 4-chloro-3-iodopyridin-2-amine (2.1 g, 65percent yield) was collected as a solid. 4-Chloro-3-iodopyridine-2-amine (5.0g, 19.0mmol, 1.0eq.), trimethyl((4-methyl-3-nitrophenyl)ethynyl)silane (5.7g, 25.0mmol, 1.25eq.), 1, 4-diazabicyclo[2.2.2]octane (3.6g, 32.3mmol, 1.7eq.) and dichlorobis(triphenylphosphine)palladium(II) (1.4g, 2.0mmol, 0.1eq.) in dry DMF (40mL) under N2 atmosphere was splitted in three microwave vials. Each vial was heated in the microwave at 145C for 2 h. EtOAc (250mL) was added and the organic phase was washed three times with aq. sat. NaHCO3-solution. The organic phase was dried over MgSO4 and solvents were removed in vacuo. The crude product was purified by flash chromatography on silica gel (cHex/EtOAc = 100:0 to 1:1) to yield the desired product A1 (3.9g, 10.8mmol, 57%) as a beige solid. 1H NMR (400MHz, d6-DMSO, 300K) delta 0.11 (s, 9H), 2.58 (s, 3H), 7.12 (d, J = 5.0 Hz, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.63 (d, J = 7.9 Hz, 1H), 7.91 (s, 1H), 8.21 (d, J = 5.0 Hz, 1H), 12.04 (s, 1H). MS (ES) C17H18ClN3O2Si requires: 359, found: 360 (M+H)+.

Molecular Weight:254.45
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:253.91077
Monoisotopic Mass:253.91077
Topological Polar Surface Area:38.9
Heavy Atom Count:9
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes