2,6-Dichloro-3,4-pyridinediamine

To a solution of intermediate 12 (37.00 g, 177.88 mmol) in HCl (60 mL) and (EtOH/H2O solution (400 mL, 1:1, v/v) was added Iron powder (30.00 g, 537.20 mmol). The reaction mixture was stirred at 100 °C for 3 hours. The reaction mixture was concentrated and diluted with water. The suspended solution was basified by aqueous NaHCO3 solution until pH=9. The precipitate was filtered and diluted in a mixture of EtOAc/MeOH (8:1, v/v). The remaining solid was filtered and the filtrate was concentrated under vacuum to afford a first batch of intermediate 13.(C) 2, 6-dichloropyridi ne-3, 4-diami neTo a solution of 2, 6-dichloro-3-nitropyridin-4-amine in ethanol (150 mL) was added iron powder (14.3 g, 0.255 mol), water (46 mL), and then concentrated HCI (28 mL). The reaction mixture was then stirred at 95 °C for 16 hours, cooled to roomtemperature, and neutralized. The precipitates were collected by filtration and dried in vacuo. The crude product was then treated with water (200 mL) and extracted with EtOAc (3 x 200 mL). The combined extracts were dried over anhydrous Na(C) 2, 6-dichloropyridi ne-3, 4-diami ne[083] To a solution of 2, 6-dichloro-3-nitropyridin-4-amine in ethanol (150 mL) was added iron powder (14.3 g, 0.255 mol), water (46 mL), and then concentrated HCI (28 mL). The reaction mixture was then stirred at 95 °C for 16 hours, cooled to room temperature, and neutralized. The precipitates were collected by filtration and dried in vacuo. The crude product was then treated with water (200 mL) and extracted with EtOAc (3 x 200 mL). The combined extracts were dried over anhydrous NaTo a solution of 2, 6-dichloro-3-nitropyridin-4-amine in ethanol (150 mL) was added iron powder (14.3 g, 0.255 mol), water (46 mL), and then concentrated HCl (28 mL). Intermediate 3: 2, 6-Dichloro-3, 4-pyridinediamine To a solution of intermediate 12 (37.00 g, 177.88 mmol) in HCl (60 mL) and (EtOH/H2O solution (400 mL, 1:1, v/v) was added Iron powder (30.00 g, 537.20 mmol). The reaction mixture was stirred at 100 C for 3 hours. The reaction mixture was concentrated and diluted with water. The suspended solution was basified by aqueous NaHCO3 solution until pH=9. The precipitate was filtered and diluted in a mixture of EtOAc/MeOH (8:1, v/v). The remaining solid was filtered and the filtrate was concentrated under vacuum to afford a first batch of intermediate 13.(C) 2, 6-dichloropyridi ne-3, 4-diami neTo a solution of 2, 6-dichloro-3-nitropyridin-4-amine in ethanol (150 mL) was added iron powder (14.3 g, 0.255 mol), water (46 mL), and then concentrated HCI (28 mL). The reaction mixture was then stirred at 95 C for 16 hours, cooled to roomtemperature, and neutralized. The precipitates were collected by filtration and dried in vacuo. The crude product was then treated with water (200 mL) and extracted with EtOAc (3 x 200 mL). The combined extracts were dried over anhydrous Na2SO4, filtered, and concentrated to afford 7.85 g of the title compound (86.5% yield).(C) 2, 6-dichloropyridi ne-3, 4-diami ne[083] To a solution of 2, 6-dichloro-3-nitropyridin-4-amine in ethanol (150 mL) was added iron powder (14.3 g, 0.255 mol), water (46 mL), and then concentrated HCI (28 mL). The reaction mixture was then stirred at 95 C for 16 hours, cooled to room temperature, and neutralized. The precipitates were collected by filtration and dried in vacuo. The crude product was then treated with water (200 mL) and extracted with EtOAc (3 x 200 mL). The combined extracts were dried over anhydrous Na2S04, filtered, and concentrated to afford 7.85 g of the title compound (86.5% yield).To a solution of 2, 6-dichloro-3-nitropyridin-4-amine in ethanol (150 mL) was added iron powder (14.3 g, 0.255 mol), water (46 mL), and then concentrated HCl (28 mL). The reaction mixture was then stirred at 95 C. for 16 hours, cooled to room temperature, and neutralized. The precipitates were collected by filtration and dried in vacuo. The crude product was then treated with water (200 mL) and extracted with EtOAc (3*200 mL). The combined extracts were dried over anhydrous Na2SO4, filtered, and concentrated to afford 7.85 g of the title compound (86.5% yield).To a solution of 2, 6-dichloro-3-nitro-pyridin-4-amine (2.6 g, 14.4 mmol) from Step A in MeOH (150 mL) was added Raney Nickel catalyst (2 g) and the reaction agitated under a hydrogen atmosphere in a Parr apparatus (35 p.s.i.) for 2 h . The reaction mixture was filtered through a pad of Celite and concentrated to yield the title compound. MS: m/z - 179 (M + 1).To a solution of 2, 6-dichloro-3-nitro-pyridin-4-amine (2.6 g, 14.4 mmol) from Step A in MeOH (150 mL) was added Raney Nickel catalyst (2 g) and the reaction agitated under a hydrogen atmosphere in a Parr apparatus (35 p.s.i.) for 2 h . The reaction mixture was filtered through a pad of Celite and concentrated to yield the title compound. MS: m/z = 179 (M + 1).To a solution of 2, 6-dichloro-3-nitro-pyridin-4-amine (2.6 g, 14.4 mmol) from Step A in MeOH (150 mL) was added Raney Nickel catalyst (2 g) and the reaction agitated under a hydrogen atmosphere in a Parr apparatus (35 p.s.i.) for 2 h . The reaction mixture was filtered through a pad of Celite and concentrated to yield the title compound. MS: m/z = 178 (M + 1).Intermediate 3: 2, 6-Dichloro-3, 4-pyridinediamine; 2, 6-dichloro-3-nitro-4-pyridinamine (881 mg, 4.24mmol) was taken up in ethanol (15ml) and tin(ll) chloride (3212mg, 16.94mmol) was added portion wise over 5min. The resulting pale yellow solution was allowed to stir at 50C under N2 for 3h, LCMS showed approx 60% conversion, the reaction was left for a further 3h, LCMS showed almost complete conversion. The reaction was allowed to cool to room temperature and was partitioned between NaHC03 (aq) (50ml) and EtOAc (50ml). The organic layer was dried using a hydrophobic frit, concentrated and dried in vacuo overnight to give the title compound as a yellow solid (734mg). LCMS (Method B): Rt = 0.57min, MH+ = 178Step B. 2, 6-Dichloro-pyridine-3, 4-diamineTo a solution of 2, 6-dichloro-3-nitro-pyridin-4-amine (2.6 g, 14.4 mmol) from Step A in MeOH (150 mL) was added Raney Nickel catalyst (2 g) and the reaction agitated under a hydrogen atmosphere in a Parr apparatus (35 p.s.i.) for 2 h . The reaction mixture was filtered through a pad of Celite and concentrated to yield the title compound. MS: m/z - 178 (M + 1).Intermediate 3: 2, 6-Dichloro-3, 4-pyridinediamine 2, 6-dichloro-3-nitro-4-pyridinamine (881 mg, 4.24 mmol) was taken up in ethanol (15 ml) and tin(II) chloride (3212 mg, 16.94 mmol) was added portion wise over 5 min. The resulting pale yellow solution was allowed to stir at 50 C. under N2 for 3 h, LCMS showed approx 60% conversion, the reaction was left for a further 3 h, LCMS showed almost complete conversion. The reaction was allowed to cool to room temperature and was partitioned between NaHCO3 (aq) (50 ml) and EtOAc (50 ml). The organic layer was dried using a hydrophobic frit, concentrated and dried in vacuo overnight to give the title compound as a yellow solid (734 mg). LCMS (Method B): Rt=0.57 min, MH+=1783, 4-Diamino-2, 6-dichloropyridine (24) A mixture of 23 (709 mg, 3.41 mmol), 4.94 g (19.33 mmol) of SnCl2.2 H2 O in 20 mL of EtOH was refluxed for 2 h. The resultant solution was rota-evaporated to remove most of the EtOH. To the residue was added H2 O (50 mL) and basified to pH 9 with 1N aq NaOH. The resulting white emulsion was extracted with CH2 Cl2 (4*50 mL). The CH2 Cl2 extract was washed with brine, dried (MgSO4), and evaporated to give 570 mg (94%) of 24 as a slight pink powder, mp 186-8 C. 1 H NMR (CDCl3) delta3.510 (bs, 2H), 4.195 (bs, 2H), 6.553 (s, 1H).

Molecular Weight:178.02
XLogP3:1.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Exact Mass:176.9860526
Monoisotopic Mass:176.9860526
Topological Polar Surface Area:64.9
Heavy Atom Count:10
Complexity:122
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes