Potassium Carbonate → 2-{1-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrrolidin-3-yl}-N,N-dimethyl-acetamide

HRID 2234661Notes

Reaction equation

HRID 2234661 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]2=[N:6][CH:7]=1.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+].[CH3:41][N:42]([CH3:51])[C:43](=[O:50])[CH2:44][CH:45]1[CH2:49][CH2:48][NH:47][CH2:46]1>[Cu]I>[CH3:18][O:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:47]3[CH2:48][CH2:49][CH:45]([CH2:44][C:43]([N:42]([CH3:41])[CH3:51])=[O:50])[CH2:46]3)[CH:3]=2)[N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:9]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 57731570N,N-dimethyl-2-pyrrolidin-3-yl-acetamideHCID 592970285-bromo-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 577316472-{1-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrrolidin-3-yl}-N,N-dimethyl-acetamideYield 30%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

A microwave reaction vial was charged with 5-bromo-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (347 mg, 0.8 mmol), copper(I)-iodide (31 mg, 0.067 mmol), proline (37 mg, 0.13 mmol), potassium carbonate (332 mg, 1.6 mmol) and N,N-dimethyl-2-pyrrolidin-3-yl-acetamide (250 mg, 1.6 mmol) obtained from step 1. The vial was flushed with nitrogen and dimethylsulfoxide (2.0 ml) was added. The reaction tube was sealed irradiated in the microwave to 140° C. for 1 hour. The crude was partitioned between ethyl acetate (20 ml) and water (20 ml). The layers were separated and the aqueous layer was extracted with ethyl acetate (10 ml). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (0% to 100% ethyl acetate in hexanes) to give 87 mg (30%) of 2-{1-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrrolidin-3-yl}-N,N-dimethyl-acetamide as a yellowish oil. MS: m/z 509.3 (M+H+).

Workup

  1. customA microwave reaction
  2. customThe vial was flushed with nitrogen and dimethylsulfoxide (2.0 ml)
  3. additionwas added
  4. customThe reaction tube was sealed
  5. customirradiated in the microwave to 140° C. for 1 hour
  6. customThe crude was partitioned between ethyl acetate (20 ml) and water (20 ml)
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with ethyl acetate (10 ml)
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography on silica gel (0% to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b3b8b12ffe724f959027d38058b20ccc
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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