(3-Methoxyphenyl)acetic acid → N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)-2-(3-methoxyphenyl)acetamide

HRID 1364516Notes

Reaction equation

HRID 1364516 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]([OH:12])=O)[CH:6]=[CH:7][CH:8]=1.C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[C:25]([C:26]#[N:27])=[C:24]([O:28][CH2:29][CH3:30])[N:23]=[C:22]([NH2:31])[CH:21]=1>C(Cl)Cl.N1C=CC=CC=1.O>[NH2:19][C:20]1[C:25]([C:26]#[N:27])=[C:24]([O:28][CH2:29][CH3:30])[N:23]=[C:22]([NH:31][C:10](=[O:12])[CH2:9][C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)[CH:21]=1

Participants

7

Reactant 3

HCID 15719(3-Methoxyphenyl)acetic acidHCID 65578Oxalyl chlorideHCID 131498684,6-Diamino-2-ethoxypyridine-3-carbonitrile

Product 1

HCID 11558900N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)-2-(3-methoxyphenyl)acetamideYield 19.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 28 mg (0.17 mmol) of (3-methoxyphenyl)acetic acid in 0.5 mL of CH2Cl2 (or the minimum amount necessary for dissolution) was added 20 μL (0.22 mmol) of oxalyl chloride. The solution was swirled, allowed to stand for 5 minutes at ambient temperature, then added to a solution of 30 mg (0.14 mmol) of 4,6-diamino-2-ethoxy-nicotinonitrile in 0.5 mL of pyridine. The mixture was shaken for 15 minutes, diluted with 1 mL of water and concentrated under reduced pressure. The residue was taken up in 3 mL of ethyl acetate, and extracted with water (2×1 mL), 1M HCl(aq.) (1×1 mL), saturated NaHCO3(aq.) (2×1 mL), and brine (1×1 mL), dried over MgSO4, filtered, and concentrated to a solid. This was recrystallized from 1 mL of methanol to provide 9 mg (16%) of a colorless solid. 1H NMR (300 MHz, d6-DMSO) 610.28 (s, 1H), 7.22 (m, 1H), 7.16 (m, 1H), 6.89 (m, 4H), 6.81 (m, 1H), 4.34 (q, 2H, J=7.1 Hz), 3.74 (s, 3H), 3.67 (s, 2H), 1.31 (t, 3H, J=7.1 Hz); MS (ESI) m/e=299 (M−Et+H)+, 327 (M+H)+, 349 (M+Na)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionextracted with water (2×1 mL), 1M HCl(aq.) (1×1 mL), saturated NaHCO3(aq.) (2×1 mL), and brine (1×1 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to a solid
  6. customThis was recrystallized from 1 mL of methanol

Sources & evidence

ORD record
ord-714745e6f56947b19cb5f6755f0d1140
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

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