* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Step c: 6-chloro-4-iodopyridin-3-amine The solution of tert-butyl 6-chloro-4-iodopyridin-3-ylcarbamate (10.0 g, 28 mmol) in 3M HCl (600 mL) was heated at 60 C. for 12 h. The mixture was allowed to cool to room temperature and treated with sat. NaHCO3 to pH=8. The aqueous layer was extracted with ethyl acetate (100 mL*3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, concentrated and purified by chromatography on silica gel (10% ethyl acetate in petroleum ether as eluant) to afford 6-chloro-4-iodopyridin-3-amine (6.6 g, 93%). 1H-NMR (CDCl3, 400 MHz) delta 7.81 (s, 1H), 7.60 (s, 1H), 4.13 (br s, 2H).
90%
(6-Chloro-4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester (3.67 g, 10.3 mmol) was dissolved in DCM (32 mL) and TFA (8 mL) was added. The reaction mixture was stirred at ambient temperature for 2 h and then evaporated in vacuo. The resultant residue was treated with 5N aqueous sodium hydroxide solution (25 mL), diluted with water (100 mL) and extracted into ethyl acetate (2 x 100 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to afford the title compound as yellow solid (2.37 g, 90%). 1H NMR (CD3OD, 300MHz): 7.80 (s, 1H), 7.60 (s, 1H), 4.14 (s, 2H). LCMS (Method B): RT = 3.00 min, M+H+ = 255.
82%
With trifluoroacetic acid; In dichloromethane; ethyl acetate;
6-Chloro-4-iodo-3-pyridinamine Trifluoroacetic acid (2.4 mL) was added to a solution of <strong>[400777-00-6]1,1-dimethylethyl (6-chloro-4-iodo-3-pyridinyl)carbamate</strong> (Description 7, 2.2 g, 6.2 mmol) in dichloromethane (50 mL) and the mixture was stirred at room temperature for 24 h. The solvent was evaporated under reduced pressure and the residue was dissolved in ethyl acetate. The mixture was washed with aqueous sodium hydroxide (1M), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluding with isohexane/EtOAc (70:30), to give the title compound as a yellow solid (1.3 g, 82%). 1H NMR (360 MHz, CDCl3) delta 7.80 (1H, s), 7.60 (1H, s), and 4.13 (2H, br s). m/z (ES+) 255, 257 (M+1).
Preparation 8 : 6-Chloro-4-io The title compound was prepared according to the method described in US 2002/0022624 Al from the compound of Preparation 7. delta? (CDCl3): 4.12 (2H, br s), 7.60 (IH, s), 7.79 (IH, s).