N,N'-Dimethylethylenediamine → tert-butyl 4-(1-ethyl-6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopiperazine-1-carboxylate

HRID 1622887Notes

Reaction equation

HRID 1622887 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([F:11])=[CH:8][CH:9]=2)[N:4]([CH2:12][CH3:13])[CH:3]=1.[O:14]=[C:15]1[NH:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]1.CNCCNC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.O1CCOCC1>[CH2:12]([N:4]1[C:5]2=[N:6][C:7]([F:11])=[CH:8][CH:9]=[C:10]2[C:2]([N:20]2[CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:16][C:15]2=[O:14])=[CH:3]1)[CH3:13]

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 678143683-bromo-1-ethyl-6-fluoro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 67817321tert-butyl 4-(1-ethyl-6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopiperazine-1-carboxylateYield 103.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

3-Bromo-1-ethyl-6-fluoro-1H-pyrrolo[2,3-b]pyridine (13.00 g, 53.48 mmol), tert-butyl 3-oxopiperazine-1-carboxylate (11.78 g, 58.83 mmol), N,N′-dimethylethane-1,2-diamine (2.36 mL, 21.93 mmol), copper(I) iodide (2.24 g, 11.77 mmol), potassium phosphate (tribasic, n-hydrate) (12.49 g, 58.83 mmol), and 1,4-dioxane (250 mL) are combined under a nitrogen atmosphere with stirring and heated to reflux overnight. The reaction is cooled, poured onto brine (ca. 500 mL) and the product extracted with CHCl3 (ca. 2×300 mL). The combined organic extracts are dried over magnesium sulphate, filtered, and concentrated in vacuo to give a yellow oil. This is purified by column chromatography on silica, eluting with 0 to 90% EtOAc in hexane, to give the title compound as an orange oil (20.039 g, 55.29 mmol). MS (m/z): 363 (M+1).

Workup

  1. temperatureheated
  2. temperatureto reflux overnight
  3. temperatureThe reaction is cooled
  4. additionpoured onto brine (ca. 500 mL)
  5. extractionthe product extracted with CHCl3 (ca. 2×300 mL)
  6. dry with materialThe combined organic extracts are dried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a yellow oil
  10. customThis is purified by column chromatography on silica
  11. washeluting with 0 to 90% EtOAc in hexane

Sources & evidence

ORD record
ord-3a0e19390872420bb9e113b08c3b4d7d
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

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