Piconol → tert-butyl 4-[1-ethyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-3-oxopiperazine-1-carboxylate

HRID 1622888Notes

Reaction equation

HRID 1622888 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9](F)=[CH:10][CH:11]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C:14]2=[O:26])=[CH:4]1)[CH3:2].[N:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH2:33][OH:34].[H-].[Na+]>CS(C)=O>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([O:34][CH2:33][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][N:27]=3)=[CH:10][CH:11]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C:14]2=[O:26])=[CH:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 11474PiconolHCID 24758Sodium hydride2×HCID 67817321tert-butyl 4-(1-ethyl-6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopiperazine-1-carboxylate

Product 1

HCID 67818259tert-butyl 4-[1-ethyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-3-oxopiperazine-1-carboxylateYield 79.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred solution of tert-butyl 4-(1-ethyl-6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopiperazine-1-carboxylate (5.00 g, 13.80 mmol) and 2-pyridine methanol (1.60 mL, 16.56 mmol) in dimethyl sulphoxide (50 mL), under a nitrogen atmosphere, is added 60% sodium hydride (0.662 g, 16.56 mmol) portionwise. The reaction is stirred at room temperature for 1 h and then heated at 135° C. overnight. The reaction is cooled to room temperature and further 60% sodium hydride (0.662 g, 16.56 mmol) added, and the reaction stirred overnight at room temperature. The reaction is 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 brown oil. This is purified by column chromatography on silica, eluting with 0 to 80% EtOAc in DCM, to give the title compound as an orange foam (4.952 g, 10.97 mmol). MS (m/z): 452 (M+1).

Workup

  1. temperatureheated at 135° C. overnight
  2. temperatureThe reaction is cooled to room temperature
  3. stirringthe reaction stirred overnight at room temperature
  4. additionThe reaction is poured 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 brown oil
  10. customThis is purified by column chromatography on silica
  11. washeluting with 0 to 80% EtOAc in DCM

Sources & evidence

ORD record
ord-8cd70ba5ca4544e9a310c09d62742b8f
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

Loading…