2,3-Diaminopyridine → N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)-2-(2,3-dimethoxyphenyl)acetamide

HRID 1364517Notes

Reaction equation

HRID 1364517 reaction equation
[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:11][C:12]([OH:14])=O.C(Cl)(=O)C(Cl)=O.[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[C:26]([O:30][CH2:31][CH3:32])[N:25]=[C:24]([NH2:33])[CH:23]=1.NC1C(N)=NC=CC=1>C(Cl)Cl.N1C=CC=CC=1>[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[C:26]([O:30][CH2:31][CH3:32])[N:25]=[C:24]([NH:33][C:12](=[O:14])[CH2:11][C:4]2[CH:5]=[CH:6][CH:7]=[C:8]([O:9][CH3:10])[C:3]=2[O:2][CH3:1])[CH:23]=1

Participants

7

Reactant 4

HCID 99562,3-DiaminopyridineHCID 65578Oxalyl chlorideHCID 1359642,3-Dimethoxyphenylacetic acidHCID 131498684,6-Diamino-2-ethoxypyridine-3-carbonitrile

Product 1

HCID 11523273N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)-2-(2,3-dimethoxyphenyl)acetamideYield 35.1%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To 67 mg (0.34 mmol) of (2,3-dimethoxyphenyl)acetic acid in 1 mL of CH2Cl2 was added 32 μL (0.37 mmol) of oxalyl chloride. The solution was stirred at ambient temperature for 20 minutes then added to a solution of 60 mg (0.28 mmol) of 4,6-diamino-2-ethoxy-nicotinonitrile in 0.5 mL of pyridine. The mixture was complete within 5 minutes though some diaminopyridine remained. The solvent was removed under reduced pressure, then the residue was taken up in 10 mL of ethyl acetate and extracted with water (2×5 mL), saturated NaHCO3(aq.) (1×5 mL), and brine (1×5 mL), dried over MgSO4, filtered, and concentrated to an oil. This was recrystallized from 8 mL of methanol to provide 35 mg (35%) of white crystals. 1H NMR (300 MHz, d6-DMSO) δ 10.22 (s, 1H), 7.15 (s, 1H), 6.97 (m, 2H), 6.88 (s, 2H), 6.81 (dd, 1H, J=7.1, 2.0 Hz), 4.35 (q, 2H, J=7.1 Hz), 3.79 (s, 3H), 3.71 (s, 2H), 3.68 (s, 3H), 1.31 (t, 3H, J=7.1 Hz); MS (ESI) m/e=327 (M−Et+H)+, 357 (M+H)+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. extractionextracted with water (2×5 mL), saturated NaHCO3(aq.) (1×5 mL), and brine (1×5 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to an oil
  6. customThis was recrystallized from 8 mL of methanol

Sources & evidence

ORD record
ord-d27b019a3c7649c6b724cdbb689e51e7
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

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