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

HRID 1364532

Reaction equation

HRID 1364532 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:5]=[C:4]([NH2:16])[CH:3]=1.[O:17]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[CH2:27][C:28](Cl)=[O:29])[CH3:18].N1C=CC=CC=1>C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:5]=[C:4]([NH:16][C:28](=[O:29])[CH2:27][C:20]2[CH:21]=[C:22]([O:25][CH3:26])[CH:23]=[CH:24][C:19]=2[O:17][CH3:18])[CH:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 596088(2,5-Dimethoxyphenyl)acetyl chlorideHCID 669206084,6-Diamino-2-phenyl-nicotinonitrile

Product 1

HCID 66920724N-(4-amino-5-cyano-6-phenylpyridin-2-yl)-2-(2,5-dimethoxyphenyl)acetamideYield 12%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 50 mg (0.24 mmol) of 4,6-diamino-2-phenyl-nicotinonitrile in 2 mL of CH2Cl2 was added 150 mg (0.70 mmol) of (2,5-dimethoxyphenyl)acetyl chloride (Example 68A), then 100 μL (1.23 mmol) of pyridine. The mixture was stirred at ambient temperature for 10 minutes then the solvent was removed under reduced pressure. The residue was taken up in 10 mL of ethyl acetate, then extracted with 1 M HCl(aq.) (2×5 mL), saturated NaHCO3(aq) (2×5 mL), and brine (1×5 mL), dried over MgSO4, filtered, and concentrated to an oil. This was purified via silica gel chromatography, eluting with 40% ethyl acetate:hexanes to provide 11 mg (12%) of a white solid. 1H NMR (300 MHz, d6-DMSO) δ 10.43 (m, 1H), 7.75 (m, 2H), 7.51 (m, 4H), 6.99 (m, 2H), 6.91 (m, 1H), 6.81 (m, 2H), 3.69 (m, 8H); MS (ESI) m/e 389 (M+H)+, 387 (M−H)−.

Workup

  1. customthe solvent was removed under reduced pressure
  2. extractionextracted with 1 M HCl(aq.) (2×5 mL), saturated NaHCO3(aq) (2×5 mL), and brine (1×5 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to an oil
  6. customThis was purified via silica gel chromatography
  7. washeluting with 40% ethyl acetate

Sources & evidence

ORD record
ord-4ceea1b837974e7aa6d452ed54598519
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Linked notes

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