N,N'-Dimethylethylenediamine → methyl 4-[1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-3-oxopiperazine-1-carboxylate

HRID 1622897Notes

Reaction equation

HRID 1622897 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[CH:8][CH:9]=2)[N:4]([CH3:19])[CH:3]=1.[O:20]=[C:21]1[NH:26][CH2:25][CH2:24][N:23]([C:27]([O:29][CH3:30])=[O:28])[CH2:22]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>O1CCOCC1.[Cu]I>[CH3:19][N:4]1[C:5]2=[N:6][C:7]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[CH:8][CH:9]=[C:10]2[C:2]([N:26]2[CH2:25][CH2:24][N:23]([C:27]([O:29][CH3:30])=[O:28])[CH2:22][C:21]2=[O:20])=[CH:3]1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 15057403Methyl 3-oxopiperazine-1-carboxylateHCID 678161163-Bromo-1-methyl-6-(2-pyridylmethoxy)pyrrolo[2,3-b]pyridine

Product 1

HCID 67815859methyl 4-[1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-3-oxopiperazine-1-carboxylateYield 80.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a solution of 3-bromo-1-methyl-6-(2-pyridylmethoxy)pyrrolo[2,3-b]pyridine (0.5 g, 1.57 mmol) in 1,4-dioxane (10 mL) is added methyl 3-oxopiperazine-1-carboxylate (0.271 g, 1.88 mmol) and potassium phosphate (0.467 g, 2.20 mmol). The mixture is degassed with nitrogen for 15 minutes, then copper(I) iodide (0.060 g, 0.31 mmol) and N,N′-dimethylethylenediamine (0.055 g, 0.63 mmol) are added. The reaction vessel is sealed and heated at 100° C. for 16 h. The reaction is cooled to room temperature, quenched with water (50 mL) and extracted with EtOAc (3×100 mL). The combined organic layers are dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue is purified by column chromatography on neutral alumina, eluting with 1% MeOH in DCM. The resultant product is triturated with Et2O/pentane (1:1) to afford the title compound (0.5 g, 1.26 mmol) as an off white solid. MS (m/z): 396 (M+1). 1H-NMR (400 MHz, DMSO-d6): δ 3.66 (s, 3H), 3.68 (s, 3H), 3.75 (m, 4H), 4.14 (s, 2H), 5.49 (s, 2H), 6.66 (d, 1H), 7.30-7.33 (m, 2H), 7.50 (d, 1H), 7.77-7.82 (m, 2H), 8.56 (d, 1H).

Workup

  1. customThe mixture is degassed with nitrogen for 15 minutes
  2. customThe reaction vessel is sealed
  3. temperatureThe reaction is cooled to room temperature
  4. customquenched with water (50 mL)
  5. extractionextracted with EtOAc (3×100 mL)
  6. dry with materialThe combined organic layers are dried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by column chromatography on neutral alumina
  10. washeluting with 1% MeOH in DCM
  11. customThe resultant product is triturated with Et2O/pentane (1:1)

Sources & evidence

ORD record
ord-e0600f2d2c2a4a3cbe87591b57ccffa6
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

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