N,N-Dimethylglycine → HCID 44199957, compound

HRID 600384Notes

Reaction equation

HRID 600384 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][N:8](COCC[Si](C)(C)C)[C:5]2=[N:6][CH:7]=1.[C:25]1([S:31]([NH2:34])(=[O:33])=[O:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CN(C)CC(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.[Cu]I>[CH3:15][C:12]([CH3:13])([CH3:14])[C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([NH:34][S:31]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)(=[O:33])=[O:32])[N:3]=2)[NH:8][CH:9]=1)=[O:16]

Participants

8

Reactant 4

HCID 673N,N-DimethylglycineHCID 7370BenzenesulfonamideHCID 62657Potassium Phosphate, TribasicHCID 578292211-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one

Product 1

HCID 44199957HCID 44199957, compoundYield 98.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
153 °C

Procedure

A mixture of 1-[2-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (0.25 g, 0.61 mmol), benzenesulfonamide (0.143 g, 0.91 mmol, 1.5 equiv.), CuI (0.023 g, 0.12 mmol, 20 mol %), N,N-dimethylglycine (0.013 g, 0.12 mmol, 20 mol %) and K3PO4 (0.323 g, 1.53 mmol, 2.5 equiv.) in DMF (2 mL) was heated under an argon atmosphere in a microwave oven at 153° C. overnight. After cooling to room temperature, the reaction mixture was diluted with H2O and extracted with DCM. The combined organic extracts was washed with H2O and concentrated. The residue was purified by flash column chromatography on silica gel with EtOAc in hexane (15% to 50% gradient over 20 min) to give 0.215 g of product as a pale yellow foam. 1H NMR (CDCl3): δ 8.50 (s, 1H), 8.29 (s, 1H), 7.99-7.96 (m, 2H), 7.61-7.47 (m, 3H), 5.67 (s, 2H), 2.64-3.58 (m, 2H), 1.38 (s, 9H), 1.00-0.94 (m, 2H), 0 (s, 9H); MS [M+H]+: 489.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with DCM
  3. washThe combined organic extracts was washed with H2O
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel with EtOAc in hexane (15% to 50% gradient over 20 min)

Sources & evidence

ORD record
ord-8f5fb4fa6b57420d96d315d27c9f9df8
Source dataset
uspto-grants-2011_03
Patent number
US07902197B2

Reaction notes

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