3-Iodo-4-pyridinamine

Off-white solid

A 2 L three-neck round-bottom flask was equipped with a mechanical stirrer, thermocouple, addition funnel, nitrogen inlet, and reflux condenser fitted with a drying tube and placed into a heating mantle. The flask was charged with glacial acetic acid (523 mL), and stirring was initiated. 4-aminopyridine (20, 95 g) was added to the reaction as a single portion, and the dissolution of the material was exothermic to 30° C. Iodine monochloride (101 mL) was added slowly over a 2 hour period at a rate to keep the internal temperature below 45° C. At the end of the addition the temperature had reached 42° C. After the complete addition of iodine monochloride, the exotherm was allowed to subside and then heating was applied to the reaction to maintain the temperature at 45-50° C. Stirring was continued at 45-50° C. overnight and continued for 10 days until the reaction was deemed to be complete, i.e., when no significant progress was being made towards product. The reaction was monitored by HPLC (MPP-LC1 (270)) by diluting an aliquot of the reaction mixture (1 mL) at various time points with (1:1) acetonitrile/water (2 mL) and submitting for analysis. The starting material eluted at 2.8 min, and the product eluted at 8.1 min. Materials used in the synthesis are detailed in Table 1. To isolate 4-amino-3-iodopyridine (21), the reaction mixture was cooled to ambient temperature and diluted with 1.9 L of water. The solution was cooled in an ice/water bath to 0-5° C. and adjusted to pH 10 with 50percent sodium hydroxide solution and strong stirring. The addition of NaOH was strongly exothermic, and ice was added if required. During the pH adjustment brown solids formed. Ethyl acetate (4 L) was added, the biphasic solution was agitated, and the layers were allowed to separate. The brown solids dissolved during the extraction, by maintaining agitation and adding more ethyl acetate if needed. The aqueous layer was extracted with fresh ethyl acetate (4 L), the biphasic solution was agitated, and the layers were allowed to separate. The combined ethyl acetate extracts were washed sequentially with 15percent sodium thiosulfate solution (2.x.2 L), water (2 L), and saturated brine solution (2 L), and then dried over sodium sulfate. The mixture was filtered through a glass microfiber filter, and the filtrate was evaporated under reduced pressure to give a brown solid. The solids were dissolved in 5percent methanol in 1 L dichloromethane (DCM) and filtered through a 2 silica plug, washing with an additional 2 L of eluent. The solution was evaporated under reduced pressure to give a brown waxy solid. The solids were dried under vacuum at ambient temperature for a minimum of 12 h.Results are shown in Table 2. 4-Amino-3-iodopyridine (21) (lot No. 1357-69-1) was a brown, waxy solid, synthesized with a yield of 173 g/78percent. 4-Amino-3-iodopyridine (21) was analyzed using HPLC, and according to results, it was 92.3percent pure. Mass spectrometry and To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice-water bath, then 4-aminopyridine (200 g, 2. 12 mol) and acetic acid (700 mL) were added in batches The mixture was then heated to reflux. Iodine ( 1 89 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 1 5 min later. After 30 min, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h, After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40percent solution of NaOH in water was added until pH > 9 Na2SO3 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed The collected solid was further purified by recrystallization in chloroform to give the desired product ( 184 g, 39percent).To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice-water bath, then 4-aminopyridine (200 g, 2. 12 mol) and acetic acid (700 mL) were added in batches The mixture was then heated to reflux. Iodine ( 1 89 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 1 5 min later. After 30 min, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h, After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40percent solution of NaOH in water was added until pH > 9 Na2SO3 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed The collected solid was further purified by recrystallization in chloroform to give the desired product ( 184 g, 39percent).Sicp.i.._3-lodopyridin-4-amine. To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice-water bath, then 4-aminopyridine (200 g, 2. 12 mol) and acetic acid (700mL) were added in batches. The mixture was then heated to reflux. Iodine (189 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four pans. One batch of iodine was added and then one batch of periodic acid dihydrate was added 15 mm later After 30 mm, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine andperiodic acid dehydrate were added, the mixture was kept refluxing for an additional3 h. After cooling to it the reaction mixture was slowly poured into water while stirring, then a 40°/b solution of NaOH in water was added until pH >9. Na2SO3 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed. The collected solid was further purified by recrystallization in chloroform to give thedesired product (1 84 g, 39percent).To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice-water bath, then 4-aminopyridine (200 g, 2. 12 mol) and acetic acid (700 mL) were added in batches The mixture was then heated to reflux. Iodine ( 1 89 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 1 5 min later. After 30 min, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h, After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40percent solution of NaOH in water was added until pH > 9 Na2SO3 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed The collected solid was further purified by recrystallization in chloroform to give the desired product ( 184 g, 39percent).[0183] Step 1. 3-Iodopyridin-4-amine. To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice- water bath, then 4-aminopyridine (200 g, 2.12 mol) and acetic acid (700 mL) were added in batches. The mixture was then heated to reflux. Iodine (189 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 15 mm later. After 30 mm, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h. After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40percent solution of NaOH in water was added until pH> 9. Na2503 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed. The collected solid was further purified by recrystallization in chloroform to give the desired product (184 g, 39percent).0191] Step 1. 3-Iodopyridin-4-amine. To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice- water bath, then 4-aminopyridine (200 g, 2.12 mol) and acetic acid (700 mL) were added in batches. The mixture was then heated to reflux. Iodine (189 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 15 min later. After 30 min, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h. After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40percent solution of NaOH in water was added until pH > 9. NaB. (3-Iodo-pyridin-4-yl)-carbamic acid tert-butyl ester Di-tert-butyl dicarbonate (20.7 g, 94.8 mmol) is added to a solution of 4-amino-3-iodo-pyridin (19.0 g, 86.4 mmol) in THF (86 mL). The resulting solution is stirred for 2 h at room temperature then concentrated to dryness. The residue is diluted with ethyl acetate and washed with saturated sodium bicarbonate solution and brine. The organic layer is dried over MgSO4, filtered and concentrated to dryness. The residue is purified by column chromatography eluding with 1% EtOAc/CH2Cl2 to give the title product and a small amount of the BOC-protected di-iodo compound. Trituration of the mixture with ether/hexane removes the undesired compound leaving the title product in the solution. Filtration of the solid and concentration of the filtrate yields the title product (18.95 g, 59.2 mmol). 1H NMR (CDCl3, 300 MHz) delta8.75(s, 1H), 8.35(d, 1H), 8.1(d, 1H), 7.0(bs, 1H), 1.55(s, 9H).A 2 L three-neck round-bottom flask was equipped with a mechanical stirrer, thermocouple, addition funnel, nitrogen inlet, and reflux condenser fitted with a drying tube and placed into a heating mantle. The flask was charged with glacial acetic acid (523 mL), and stirring was initiated. 4-aminopyridine (20, 95 g) was added to the reaction as a single portion, and the dissolution of the material was exothermic to 30 C. Iodine monochloride (101 mL) was added slowly over a 2 hour period at a rate to keep the internal temperature below 45 C. At the end of the addition the temperature had reached 42 C. After the complete addition of iodine monochloride, the exotherm was allowed to subside and then heating was applied to the reaction to maintain the temperature at 45-50 C. Stirring was continued at 45-50 C. overnight and continued for 10 days until the reaction was deemed to be complete, i.e., when no significant progress was being made towards product. The reaction was monitored by HPLC (MPP-LC1 (270)) by diluting an aliquot of the reaction mixture (1 mL) at various time points with (1:1) acetonitrile/water (2 mL) and submitting for analysis. The starting material eluted at 2.8 min, and the product eluted at 8.1 min. Materials used in the synthesis are detailed in Table 1. To isolate To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice-water bath, then 4-aminopyridine (200 g, 2. 12 mol) and acetic acid (700 mL) were added in batches The mixture was then heated to reflux. Iodine ( 1 89 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 1 5 min later. After 30 min, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h, After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40% solution of NaOH in water was added until pH > 9 Na2SO3 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed The collected solid was further purified by recrystallization in chloroform to give the desired product ( 184 g, 39%).To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice-water bath, then 4-aminopyridine (200 g, 2. 12 mol) and acetic acid (700 mL) were added in batches The mixture was then heated to reflux. Iodine ( 1 89 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 1 5 min later. After 30 min, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h, After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40% solution of NaOH in water was added until pH > 9 Na2SO3 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed The collected solid was further purified by recrystallization in chloroform to give the desired product ( 184 g, 39%).Sicp.i.._3-lodopyridin-4-amine. To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice-water bath, then 4-aminopyridine (200 g, 2. 12 mol) and acetic acid (700mL) were added in batches. The mixture was then heated to reflux. Iodine (189 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four pans. One batch of iodine was added and then one batch of periodic acid dihydrate was added 15 mm later After 30 mm, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine andperiodic acid dehydrate were added, the mixture was kept refluxing for an additional3 h. After cooling to it the reaction mixture was slowly poured into water while stirring, then a 40/b solution of NaOH in water was added until pH >9. Na2SO3 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed. The collected solid was further purified by recrystallization in chloroform to give thedesired product (1 84 g, 39%).To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice-water bath, then 4-aminopyridine (200 g, 2. 12 mol) and acetic acid (700 mL) were added in batches The mixture was then heated to reflux. Iodine ( 1 89 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 1 5 min later. After 30 min, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h, After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40% solution of NaOH in water was added until pH > 9 Na2SO3 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed The collected solid was further purified by recrystallization in chloroform to give the desired product ( 184 g, 39%).[0183] Step 1. 3-Iodopyridin-4-amine. To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice- water bath, then 4-aminopyridine (200 g, 2.12 mol) and acetic acid (700 mL) were added in batches. The mixture was then heated to reflux. Iodine (189 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 15 mm later. After 30 mm, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h. After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40% solution of NaOH in water was added until pH> 9. Na2503 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed. The collected solid was further purified by recrystallization in chloroform to give the desired product (184 g, 39%).0191] Step 1. 3-Iodopyridin-4-amine. To a 2 L 3-necked flask was added a solution of 38 mL of concentrated sulfuric acid in 200 mL water. The solution was cooled with an ice- water bath, then 4-aminopyridine (200 g, 2.12 mol) and acetic acid (700 mL) were added in batches. The mixture was then heated to reflux. Iodine (189 g, 0.745 mol) and periodic acid dihydrate (97 g, 0.424 mol) were both equally divided into four parts. One batch of iodine was added and then one batch of periodic acid dihydrate was added 15 min later. After 30 min, a new batch of iodine and periodic acid dihydrate were added in the same way. When all four batches of iodine and periodic acid dehydrate were added, the mixture was kept refluxing for an additional 3 h. After cooling to rt the reaction mixture was slowly poured into water while stirring, then a 40% solution of NaOH in water was added until pH > 9. Na2S03 was added to destroy the unreacted iodine. After cooling to rt, a filtration was performed. The collected solid was further purified by recrystallization in chloroform to give the desired product (184 g, 39%).To a solution of 4-aminopyridine (1a, 37.65 g, 0.4 mole) in HOAc (200 mL) was added iodine monchloride (130 g, 0.8 mole) portionwise. The reaction mixture was stirred at 45 C. for 20 h, then diluted with water (500 mL). The mixture was cooled to 0 C., and basified 30% NaOH to pH=9-10. The solution was extracted with EtOAc (1 L×2) and the combined extracts were washed with 15% Na2S2O3 (400 mL×2), water, brine, dried over Na2SO4, and evaporated in vacuo to give 1b (62 g) as a light yellow solid. ES-MS m/z 221 (MH+). [0185] Into a pressure flask was added 1b (4.4 g, 20 mmol), cupric iodide (228 mg, 1.2 mmol), (trimethylsilyl)acetylene (7.08 g, 72 mmol), triethylamine (200 mL) and DMF (80 mL). The mixture was stirred under nitrogen for 10 min, followed by addition of Pd(PPh3)2Cl2 (0.84 g, 1.2 mmol). The mixture was then stirred to 70 C. for 5 h, and then diluted with ethyl acetate (600 mL). The solution was washed with H2O (250 mL×2), brine (250 mL), dried over Na2SO4, and evaporated in vacuo to give crude product which was purified by flash chromatography (100% CH2Cl2 to 2% MeOH in CH2Cl2) to afford Compound 1c (2. 97 g, 78%) as a light brown solid. 1H NMR (CDCl3) delta 8.37 (s, 1H), 8.13 (d, J=5.7 Hz, 1H), 6.53 (d, J=5.6 Hz, 1H), 4.67 (bs, 2H), 0.27 (s, 9H). ES-MS m/z 191 (MH+). [0186] Into an ice-cold solution of 1c (1.35 g, 7.1 mmol) in THF (50 mL) was added 95% NaH (1.86 g, 8.5 mmol). The mixture was stirred at 0 C. for 10 min, rt for 10 min, then cooled back to 0 C. (Boc)2O (1.86 g, 8.5 mmol) was added and the mixture was stirred at 0 C. for 30 min and then rt for 2 h. Additional 95% NaH (0.08 g, 3.5 mmol) and (Boc)2O (0.2 g, 0.92 mmol) were added and the mixture was stirred at rt for another 2 h. The reaction was then quenched slowly with saturated NaHCO3 (10 mL), extracted with ethyl acetate (200 mL×2). The organic layer was washed with brine, dried over Na2SO4, and evaporated in vacuo. The crude product was purified by flash chromatography (EtOAc/hexane; 1:3) to give 1d (0.67 g). ES-MS m/z 219 (MH+). [0187] To a solution of 1d (1.3 g, 4.5 mmol) in DMF (20 mL) was added cupric iodide (0.85 g, 4.5 mmol). The mixture was stirred at 80 C. for 6 h and then filtered. The filtrate was extracted with ethyl acetate (100 mL×3), and the organic layer was washed with H2O, brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (Ethyl acetate/hexane; 1:3) to give Compound 1e (0.25 g, 26%). 1H NMR (CDCl3) delta 8.89 (s, 1H), 8.47 (d, J=5.8 Hz, 1H), 7.98 (d, J=5.7 Hz, 1H), 7.62 (d, J=3.7 Hz, 1H), 6.66 (d, J=3.7 Hz, 1H), 1.69 (s, 9H). ES-MS m/z 219 (MH+). [0188] To a solution of 1e (0.178 g, 0.82 mmol) in methylene chloride (5 mL) was added TFA (1.0 mL) slowly. The mixture was stirred at rt for 1.5 h, and The solvent was evaporated to obtain 5-azaindole 1f as a white solid (0.18 g, 95%). 1H NMR (CDCl3) delta 8.97 (s, 1H), 8.31 (d, J=5.7 Hz, 1H), 7.35 (d, J=5.7 Hz, 1H), 7.29 (m, 1H), 6.68 (d, J=3.3 Hz, 1H). ES-MS m/z 119 (MH+). [0189] A mixture of Compound 1f (0.26 g, 2.2 mmol) and cesium carbonate (1.43 g, 4.4 mmol) in DMF (10 mL) was stirred at rt for 10 min, and then 3-methoxypropylbromide (0.40 g, 2.64 mmol) was added. The reaction mixture was stirred at 60 C. for 3 h. The solvent was evaporated and the residue was partitioned between EtOAc (150 mL) and water (100 mL). The organic layer was washed with water (3×50 mL), brine (2×50 mL), then dried (Na2SO4) and evaporated in vacuo to give a brown oil. The crude product was purified by flash column chromatography (from 100% DCM to DCM/MeOH/NH4OH; 97:3:0.3) to afford Compound 1g (0.26 g, 62%) as light brown oil. 1H NMR (CDCl3) delta 8.91 (s, 1H), 8.31 (d, J=5.8 Hz, 1H), 7.27 (s, 1H), 7.11 (d, J=3.2 Hz, 1H), 6.60 (d, J=3.3 Hz, 1H), 4.25 (t, J=6.7 Hz, 2H), 3.32 (s, 3H), 3.25 (t, J=5.7 Hz, 2H), 2.05 (m, 2H). ES-MS m/z 191(MH+). [0190] Oxalyl chloride (3 mL) was added slowly to a solution of compound 1g (0.22 g, 1.14 mmol) in ether (5 mL). The mixture was heated to 48 C. in a pressure tube overnight. TLC shown that some starting materials were still present. Additional 0.5 mL of oxalyl chloride was added and stirring was continuted at 48 C. for another night. The mixture was then cooled down to rt, to which methanol (3 mL) was added. The mixture was heated to 48 C. and stirred for 2 h. The volatiles removed under vacuo and the residue was purified by flash chromatography (from 100% DCM to DCM/MeOH/NH4OH; 97:3:0.3) to afford Compound 1h (0.15 g, 48%) as a white solid. 1H NMR (CDCl3) delta 8.51 (d, J=5.8 Hz, 1H), 8.44 (s, 1H), 7.37 (m, 1H), 4.34 (t, J=6.8 Hz, 2H), 3.97 (s, 3H), 3.35 (s, 3H), 3.30 (t, J=5.7 Hz, 2H), 2.12 (m, 2H). ES-MS m/z 277 (MH+). [0191] The alpha-ketoester Compound 1h (53.8 mg, 0.20 mmol) and amide Compound 1i (23 mg, 0.14 mmol) were combined in dry THF (3 mL) under argon and cooled with an ice bath as a solution of 1.0 M potassium t-butoxide in THF (1 mL, 1 mmol) was added dropwise. The mixture was stirred at 0 C. for 30 ...A. 3-Iodopyridin-4ylamine. A solution of potassium iodide (19.48 g, 117.4 mmol) and iodine (18.37 g, 72.3 mmol) in water (77 ML) is added dropwise via an addition funnel to a refluxing solution of 4-aminopyridine (9.21 g, 97.8 mmol) and sodium carbonate (6.12 g, 57.7 mmol) in water (35 ML).Upon complete addition the mixture is stirred for 2 hours at reflux then cooled to room temperature and extracted with ethyl acetate.The combined organic layers are washed with saturated sodium thiosulfate solution (3*) and brine then dried over MgSO4, filtered and concentrated to give the title product (8.37 g, 38.0 mmol) and a trace of the di-iodo compound as an yellow/orange solid.This material is used in the subsequent step without further purification. 1H NMR (CDCl3, 300 MHz) delta8.70 (s, 1H), 8.10 (d, 1H), 6.55 (d, 1H), 4.60 (bs, 2H).4-Aminopyridine (40.5 g, 0.4303 mol) was placed in a 1 L 3-neck flask and thenNa2CO3 (22.78 g, 0.2150 mmol) and water (100 mL) was added. The mixture was heated to reflux and stirred for 5 minutes. Iodine (81.84 g, 0.3224 mol) and potassium iodide (71.36 g, 0.4301 mol) were dissolved in water (500 mL) and placed in an addition funnel. The iodide/potassium iodide/water mixture was added to the reaction dropwise while the mixture continued to be heated and stirred. An additional 0.25 equiv of the iodide/potassium iodide/water mixture was prepared and added to the reaction mixture. The mixture was heated and stirred for 8 hours and then allowed to cool to room temperature. Ethyl acetate was added and the mixture was washed with water, Na2S2O3, and brine. The organic layer was separated, dried (Na2SO4), filtered, and concentrated. The residue was dissolved in dichloromethane and filtered using a silica plug (30% EtOAc / 70% hexane system, followed by 100% EtOAc system). The filtrate was dried under reduced pressure to give 4-amino-3- iodopyridine (27.0 g, 29%) as a beige solid.3-Iodo-4-pyridinamine Prepared from 4-pyridinamine according to the method of Description 3. 1H NMR (250 MHz, CDCl3) delta 8.56 (1H, s), 8.10 (1H, d, J 5.5 Hz), 6.60 (1H, d, J 5.5 Hz), and 4.75 (2H, br s).A.

Molecular Weight:220.01
XLogP3:0.8
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