Dimethylformamide → N-(4-amino-5-cyano-6-propylpyridin-2-yl)acetamide

HRID 1364526Notes

Reaction equation

HRID 1364526 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](Br)[N:5]=[C:4]([NH:11][C:12](=[O:14])[CH3:13])[CH:3]=1.[C:15]1(C)[CH:20]=CC=C[C:16]=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CN(C=O)C.[I-].C([Zn+])CC>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH2:16][CH2:15][CH3:20])[N:5]=[C:4]([NH:11][C:12](=[O:14])[CH3:13])[CH:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 80271Tri-o-tolylphosphineHCID 11557905N-(4-Amino-6-bromo-5-cyano-pyridin-2-yl)-acetamideHCID 178455873HCID 178455873, compound

Product 1

HCID 11680140N-(4-amino-5-cyano-6-propylpyridin-2-yl)acetamideYield 159%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To 128 mg of N-(4-amino-6-bromo-5-cyano-pyridin-2-yl)-acetamide (Example 65A), 6 mg (0.027 mmol) of palladium(II)acetate, and 30 mg (0.098 mmol) of tri(o-tolyl)phosphine was added 0.5 mL of DMF. The mixture was put under N2 and stirred, then 2.0 mL of the n-propylzinc iodide solution was added via syringe. The mixture was heated at 90° C. for 10 minutes then poured into a stirred mixture of 10 mL water and 10 mL ethyl acetate. The metal salts were filtered away through diatomaceous earth, then the layers were separated. The organic layer was extracted with water (2×10 mL), and brine (1×10 mL), dried over MgSO4, filtered, and concentrated to a solid. This was purified via silica gel chromatography, eluting with 50:50 hexanes:ethyl acetate and loading as a solution in hot ethyl acetate to provide 34 mg (31%) of a white solid. 1H NMR (300 MHz, d6-DMSO) δ 10.29 (s, 1H), 7.39 (s, 1H), 6.82 (s, 2H), 2.63 (m, 2H), 2.07 (m, 3H), 1.67 (m, 2H), 0.92 (t, 3H, J=7.5 Hz); MS (ESI) m/e 219 (M+H)+; m/e 217 (M−H)−.

Workup

  1. filtrationThe metal salts were filtered away through diatomaceous earth
  2. customthe layers were separated
  3. extractionThe organic layer was extracted with water (2×10 mL), and brine (1×10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to a solid
  7. customThis was purified via silica gel chromatography
  8. washeluting with 50:50 hexanes

Sources & evidence

ORD record
ord-869d449a48bb4f7b934b1077e57ca5ed
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

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