Dimethylformamide → HCID 59278503, compound

HRID 2067984Notes

Reaction equation

HRID 2067984 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[CH:26]=[C:25]([C@@H:27]([NH:30][S:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])[CH2:28][CH3:29])[CH:24]=[CH:23][N:22]=1.[CH3:37][N:38](C)C=O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[C-]#N.[Zn+2].[C-]#N>[C:37]([C:21]1[CH:26]=[C:25]([C@@H:27]([NH:30][S:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])[CH2:28][CH3:29])[CH:24]=[CH:23][N:22]=1)#[N:38]

Participants

6

Reactant 3

HCID 6228Dimethylformamide2×HCID 11776TriphenylphosphineHCID 86657766HCID 86657766, compound

Product 1

HCID 59278503HCID 59278503, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
140 °C

Procedure

Triphenylphosphine (PS-resin bound, 287 mg) and palladium acetate (70 mg, 0.31 mmol) were combined in a pressure vial. Dimethylformamide (3 mL) was added. The vial was flushed with nitrogen and a septa was affixed. The mixture was stirred at room temp. for 1 h, then the septa was removed and zinc cyanide (367 mg, 3.13 mmol) was added, followed by 2-methylpropane 2-sulfinic acid [(S)-1-(2-bromo-pyridin-4-yl)-propyl]-amide (1.00 g, 3.13 mmol) in dimethylformamide (7 mL). The vial was again flushed with nitrogen and sealed. The reaction was allowed to heat at 140° C. in an oil bath for 1 h. The solids are filtered of using a glass frit and rinsed with diethylether. The filtrate was diluted with diethylether and extracted with water (2×40 mL) and with brine (40 mL). The organic phase was dried with sodium sulfate and concentrated. The residue was purified by prepHPLC (eluted with 15-85% acetonitrile in water, with 0.1% TFA). Fractions were concentrated to remove acetonitrile, basified by sat. sodium bicarbonate solution, extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered, and concentrated to yield 2-methyl-propane-2-sulfinic acid [(S)-1-(2-cyano-pyridin-4-yl)-propyl]-amide as a colorless oil (460 mg, 55%).

Workup

  1. customThe vial was flushed with nitrogen
  2. customthe septa was removed
  3. customThe vial was again flushed with nitrogen
  4. customsealed
  5. filtrationThe solids are filtered
  6. washrinsed with diethylether
  7. additionThe filtrate was diluted with diethylether
  8. extractionextracted with water (2×40 mL) and with brine (40 mL)
  9. dry with materialThe organic phase was dried with sodium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by prepHPLC (eluted with 15-85% acetonitrile in water, with 0.1% TFA)
  12. concentrationFractions were concentrated
  13. customto remove acetonitrile
  14. extractionextracted with ethyl acetate
  15. washwashed with brine
  16. dry with materialdried over sodium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated

Sources & evidence

ORD record
ord-9719e49e504e4d698672d75cdd105ed5
Source dataset
uspto-grants-2012_10
Patent number
US08293917B2

Reaction notes

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