1,3-Propanediamine → 2-Amino-5-iodo-6-pentoxycarbonylpyridine

HRID 1984580Notes

Reaction equation

HRID 1984580 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[C:4]([C:9]([O:11][CH3:12])=[O:10])[N:3]=1.NCCCN.[I-:18].[Na+].[CH2:20](O)[CH2:21][CH2:22][CH2:23]C>O.[Cu]I>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([I:18])=[C:4]([C:9]([O:11][CH2:12][CH2:20][CH2:21][CH2:22][CH3:23])=[O:10])[N:3]=1

Participants

7

Reactant 4

HCID 4281,3-Propanediamine2×HCID 5238Sodium Iodide2×HCID 62761-PentanolHCID 10657127Methyl 6-amino-3-bromopyridine-2-carboxylate

Product 1

HCID 577182862-Amino-5-iodo-6-pentoxycarbonylpyridine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 962WaterSolvent

Conditions

Temperature
135 °C

Procedure

To a stirred solution of 2-amino-5-bromo-6-methoxycarbonylpyridine (13.8 g, 59.3 mmol) in n-pentanol (75 mL) was added 1,3-diaminopropane (900 mg, 12.1 mmol), copper (I) iodide (1.15 g, 6.0 mmol) and sodium iodide (18.0 g, 120 mmol). The reaction mixture heated to 135° C. After 16 hours (HPLC analysis shows ˜70% conversion), further portions of copper (I) iodide (600 mg, 3.0 mmol), sodium iodide (9.0 g, 60 mmol) and 1,3-diaminopropane (450 mg, 6.0 mmol) were added. After a further 4 hours, the reaction mixture was cooled to room temperature, diluted with water (200 mL), and extracted with ethyl acetate (2×200 mL). The combined organic extracts were dried over magnesium sulphate and concentrated under reduced pressure. Filtration through a short plug of silica, washing with ethyl acetate:cyclohexane 1:2 affords 2-amino-5-iodo-6-npentyloxycarbonylpyridine (8.94 g, 26.7 mmol, 45%) as a pale yellow solid. 1H NMR (CDCl3) 7.82 (1H, d, J 12 Hz, C4-H), 6.36 (1H, d, J 12 Hz, C3-H), 4.65 (2H, m, NH2), 4.36 (2H, d, J 8 Hz, COCH2), 1.87-0.89 (9H, m, CH2CH2CH2CH3)

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (2×200 mL)
  3. dry with materialThe combined organic extracts were dried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. filtrationFiltration through a short plug of silica
  6. washwashing with ethyl acetate:cyclohexane 1:2
  7. customaffords 2-amino-5-iodo-6-npentyloxycarbonylpyridine (8.94 g, 26.7 mmol, 45%) as a pale yellow solid

Sources & evidence

ORD record
ord-df4689a1bd824bae992fe13631c9e263
Source dataset
uspto-grants-2009_06
Patent number
US07544702B2

Reaction notes

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