Pyridine → N-(4-amino-5-cyano-6-propylpyridin-2-yl)-2-(2,5-dimethoxyphenyl)acetamide

HRID 1364530Notes

Reaction equation

HRID 1364530 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH2:10][CH2:11][CH3:12])[N:5]=[C:4]([NH2:13])[CH:3]=1.N1C=CC=CC=1.[O:20]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1[CH2:30][C:31](Cl)=[O:32])[CH3:21]>C(Cl)Cl.O>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH2:10][CH2:11][CH3:12])[N:5]=[C:4]([NH:13][C:31](=[O:32])[CH2:30][C:23]2[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:22]=2[O:20][CH3:21])[CH:3]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 596088(2,5-Dimethoxyphenyl)acetyl chlorideHCID 19371862HCID 19371862, compound

Product 1

HCID 66920619N-(4-amino-5-cyano-6-propylpyridin-2-yl)-2-(2,5-dimethoxyphenyl)acetamideYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 23 mg (0.13 mmol) of 4,6-diamino-2-propyl-nicotinonitrile (Example 68B) and 50 mg (0.63 mmol) of pyridine in 1 mL of CH2Cl2 was added 35 mg (0.16 mmol) of (2,5-dimethoxyphenyl)acetyl chloride (Example 68A). The mixture was stirred at ambient temperature for 10 minutes then diluted with 3 mL of water. The mixture was extracted with ethyl acetate (3×3 mL), then the combined ethyl acetate layers were back extracted with saturated NaHCO3(aq.) (1×3 mL), and brine (1×3 mL), dried over MgSO4, filtered, and concentrated to an oil. This was suspended in 5 mL of toluene, then concentrated under reduced pressure to remove some pyridine. The product was purified via silica gel chromatography, eluting with 60:40 ethyl acetate:hexanes to provide 21 mg (46%) of a white solid. 1H NMR (300 MHz, d6-DMSO) δ 10.27 (s, 1H), 7.34 (s, 1H), 6.83 (m, 5H), 3.70 (m, 6H), 3.65 (s, 2H), 2.64 (m, 2H), 1.68 (m, 2H), 0.93 (t, 3H, J=7.3 Hz); MS (ESI) m/e 355 (M+H)+, 353 (M−H)−.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (3×3 mL)
  2. extractionthe combined ethyl acetate layers were back extracted with saturated NaHCO3(aq.) (1×3 mL), and brine (1×3 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to an oil
  6. concentrationconcentrated under reduced pressure
  7. customto remove some pyridine
  8. customThe product was purified via silica gel chromatography
  9. washeluting with 60:40 ethyl acetate

Sources & evidence

ORD record
ord-bac24606f184438f8cc1833cb229ae44
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

Loading…