2,6-Diaminopyridine → HCID 69135947, compound

HRID 968442Notes

Reaction equation

HRID 968442 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH2:8])[N:3]=1.F[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1.[H-].[Na+].[NH4+].[Cl-]>CN(C=O)C>[N+:16]([C:13]1[CH:14]=[CH:15][C:10]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([NH2:8])[N:3]=2)=[CH:11][CH:12]=1)([O-:18])=[O:17]

Participants

6

Reactant 4

HCID 88612,6-DiaminopyridineHCID 9590p-FluoronitrobenzeneHCID 24758Sodium hydrideHCID 25517Ammonium Chloride

Product 1

HCID 69135947HCID 69135947, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,6-Diaminopyridine (9.2 mmol, 1.0 g) and 1-fluoro-4-nitrobenzene (9.2 mmol, 1.3 g) were dissolved in 10 mL anhydrous DMF. The solution was stirred at ambient temperature while 95% sodium hydride (18.3 mmol, 440 mg) was added. The solution turned reddish black in 30 min. The reaction mixture was stirred for an additional 20 hours at room temperature. The reaction mixture was poured slowly into 25 mL 10% aqueous NH4Cl solution mixed with ice (25 g). The resulted aqueous solution was extracted with EtOAc (4×30 mL). The combined organic phase was dried over MgSO4 and evaporated to dryness. The residual oil was purified by flash column chromatography on silica gel (EtOAc:Hexane 1:2) to provide N2-(4-nitrophenyl)pyridine-2,6-diamine (1.6 g, 76%), a reddish orange crystal: 1H NMR (500 MHz, CDCl3) δ 8.19 (d, 2H, J=9.0 Hz), 7.51 (d, 2H, J=9.0 Hz), 7.42 (t, 1H, J=8.0 Hz), 6.85 (s, 1H), 6.30 (d, 1H, J=8.0 Hz), 6.16 (d, 1H, J=8.0 Hz), 4.51 (s, 2H); MS m/z (relative intensity) 231 (M+1, 100), 184 (100). N2-(4-nitrophenyl)pyridine-2,6-diamine (2.6 mmol, 0.6 g) and 10% Pd/C (30 mg) were added to a 20 mL test tube equipped with a stir bar and then dry ice (0.5 g, CO2) was added to the mixture just before MeOH (8 mL) was added. The suspension was then put into a pressure vessel under 80 psi H2. The reaction mixture was stirred for 3 hours. The solution turned from yellow to colorless. The reaction mixture was transferred into a 10 mL syringe and filtered through an Acrodisc syringe Filter into a 100 mL round bottom flask containing 37% aqueous HCl (4 mL). The solvent was then evaporated and azeotroped to dryness with toluene and absolute ethanol (3×30 mL of 1:1 mixture). The product was obtained as an off-white powder in quantitative yield: 1H NMR (500 MHz, D2O) δ 7.48 (t, 1H, J=14.0 Hz), 7.25 (m, 4H), 6.13 (d, 1H, J=14.0 Hz), 6.09 (d, 1H, J=14.0 Hz); Ms m/z (relative intensity) 201 (M+1, 100).

Workup

  1. additionwas added
  2. extractionThe resulted aqueous solution was extracted with EtOAc (4×30 mL)
  3. dry with materialThe combined organic phase was dried over MgSO4
  4. customevaporated to dryness
  5. customThe residual oil was purified by flash column chromatography on silica gel (EtOAc:Hexane 1:2)

Sources & evidence

ORD record
ord-b95836c345c147d4b284525470aff473
Source dataset
uspto-grants-2007_12
Patent number
US07303592B2

Reaction notes

Loading…