3-Iodopyridin-2-amine

Light yellow Needles

3-Iodopyridin-2-amine In a flask fitted with a mechanical stirrer, a Dean Stark trap and condenser was added 7a (800 g, 2.63 mol) and 3N hydrochloric acid (8 L). The solution was heated at reflux for 10 hours as the pivalic acid was distilled off. The reaction was cooled to ambient temperature and neutralized by the addition of 50percent sodium hydroxide to a pH of 8. The mixture was extracted with ethyl acetate (2.x.8 L), the organics dried over sodium sulfate and the solvent removed under reduced pressure. The residue was purified by Kugelrohr distillation to give 8a as an off-white solid. Yield: 520 g, 90percent.Manufacturing Example 1-2-1 3-Iodopyridin-2-ylamine; A mixture of N-(3-lodopyridin-2-yl)-2, 2-dimethyl-propionamide (66.2 g, 218 mmol) described in Manufacturing Example 39-1-2, 5 N aqueous sodium hydroxide solution (200 mL) and methanol (200 mL) was stirred under reflux for 1 hour and 20 minutes. The reaction solution was allowed to room temperature and partitioned into water and ethyl acetate. The aqueous layer was extracted with ethyl acetate three times. The organic layers were combined, washed with saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. The sodium sulfate was removed by filtration, and the solvent was concentrated under a reduced pressure to obtain the title compound (41.2 g, 85.9percent).A mixture of N-(3-Iodopyridin-2-yl)-2, 2-dimethyl-propionamide (66.2 g, 218 mmol) described in Manufacturing Example 39-1-2, 5 N aqueous sodium hydroxide solution (200 mL) and methanol (200 mL) was stirred under reflux for 1 hour and 20 minutes. The reaction solution was allowed to room temperature and partitioned into water and ethyl acetate. The aqueous layer was extracted with ethyl acetate three times. The organic layers were combined, washed with saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. The sodium sulfate was removed by filtration, and the solvent was concentrated under a reduced pressure to obtain the title compound (41.2 g, 85.9percent). Manufacturing Example 1-2-3 Step 1: 3-(4-methyl-3-nitrophenyl)-2-(trimethylsilyl)-1H-pyrrolo[2, 3-b]pyridine (E1) 2-Amino-3-iodopyridine (5.65g, 25.71mmol, 1.2eq.), trimethyl((4-methyl-3-nitrophenyl)ethynyl)silane (5.00g, 21.43mmol, 1.0eq.), 1, 4-diazabicyclo[2.2.2]octane (4.08g, 32.3mmol, 1.7eq.) and dichlorobis(triphenylphosphine)palladium(II) (1.51g, 2.14mmol, 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 (DCM/MeOH = 100:0 to 10:1) to yield the desired product E1 (4.96g, 10.25mmol, 71%) as an orange solid. MS (ES) C17H19N3O2Si requires: 325, found: 326 (M+H)+.4-chloro-N-(4-((4-methylpiperazin-1-yl)methylene)-3-(trifluoromethyl)phenyl)-3-((trimeth ylsilyl)ethynyl)benzamide (320 mg, 0.63 mmol), 4-chloro-N-(4-((4-methylpiperazin-1-yl)methylene)-3-(trifluoromethyl)phenyl)-3-((Trimet hylsilyl)ethynyl)benzamide (320 mg, 0.63 mmol),

Molecular Weight:220.01
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:219.94975
Monoisotopic Mass:219.94975
Topological Polar Surface Area:38.9
Heavy Atom Count:8
Complexity:76.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes