Pyridine → tert-Butyl 3-iodo-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

HRID 1625426Notes

Reaction equation

HRID 1625426 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.N1C=CC=CC=1.[I:16]Cl.O1CCOCC1.[C:24]([O:28][C:29]([O:31]C(OC(C)(C)C)=O)=O)([CH3:27])([CH3:26])[CH3:25].CN(C)CCN>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:24]([O:28][C:29]([N:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([I:16])=[CH:2]1)=[O:31])([CH3:27])([CH3:26])[CH3:25]

Participants

9

Reactant 6

HCID 1049PyridineHCID 92221H-Pyrrolo(2,3-b)pyridineHCID 24640Iodine chlorideHCID 312751,4-DioxaneHCID 66053N,N-DimethylethylenediamineHCID 90495Di-tert-butyl dicarbonate2×

Product 1

HCID 23529164tert-Butyl 3-iodo-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

1H-Pyrrolo[2,3-b]pyridine (2.00 g, 0.0169 mol; Aldrich) was dissolved in pyridine (17 mL, 0.21 mol; Acros) and cooled in an ice bath. A solution of 1.00 M of iodine monochloride in methylene chloride (18.6 mL; Aldrich) was added over 5 min. After 15 min the cooling bath was removed, and after another 30 min the solution was diluted with 200 mL of ethyl acetate. The organic solution was washed sequentially with 1 N hydrogen chloride and 1 N sodium hydroxide, dried over magnesium sulfate, and concentrated. The material was dissolved in 1,4-dioxane (85 mL, 1.1 mol; Acros) and treated with di-tert-butyldicarbonate (4.07 g, 0.0186 mol; Aldrich) and 4-dimethylaminopyridine (0.216 g, 0.00177 mol; Aldrich). The mixture was stirred at room temperature for 3 days. Excess di-tert-butyldicarbonate was destroyed by the addition of N,N-dimethyl-1,2-ethanediamine (1.7 mL, 0.015 mol). After stirring for 30 min, the solution was evaporated to dryness, taken up in ethyl acetate, then washed with dilute HCl and then saturated NaCl, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography produced the title compound in 2.03 g (35%) yield. MS m/z=345.01 (M+1). 1H NMR (400 MHz, CDCl3)™ ppm 8.527 (dd, J=4.8, 1.5 Hz, 1H) 7.796 (s, 1H) 7.717 (dd, J=7.9, 1.5 Hz, 1H) 7.276 (dd, J=7.9, 4.8 Hz, 1H) 1.671 (s, 9H). TLC Rf=0.50 in 3:1 hexanes/ethyl acetate.

Workup

  1. temperaturecooled in an ice bath
  2. customAfter 15 min the cooling bath was removed
  3. additionafter another 30 min the solution was diluted with 200 mL of ethyl acetate
  4. washThe organic solution was washed sequentially with 1 N hydrogen chloride and 1 N sodium hydroxide
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. stirringAfter stirring for 30 min
  8. customthe solution was evaporated to dryness
  9. washwashed with dilute HCl
  10. dry with materialsaturated NaCl, dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-51b4fedd0e6b4b8d800ea26e4f9c77e5
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

Loading…