Ethylene Glycol → N-cyclopropyl-3-(3-fluoro-4-methylphenyl)-3H-imidazo[4,5-b]pyridine-2-carboxamide

HRID 2272693Notes

Reaction equation

HRID 2272693 reaction equation
[CH:1]1([NH:4][C:5](=[O:24])[C:6]([NH:8][C:9]2[C:10]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([F:23])[CH:17]=3)=[N:11][CH:12]=[CH:13][CH:14]=2)=O)[CH2:3][CH2:2]1.C(O)CO>O.[OH-].[Na+]>[CH:1]1([NH:4][C:5]([C:6]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([F:23])[CH:17]=3)[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[N:8]=2)=[O:24])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 174Ethylene GlycolHCID 86730063N-cyclopropyl-N'-{2-[(3-fluoro-4-methylphenyl)amino]pyridin-3-yl}ethanediamide

Product 1

HCID 78322288N-cyclopropyl-3-(3-fluoro-4-methylphenyl)-3H-imidazo[4,5-b]pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
200 °C

Procedure

A mixture of N-cyclopropyl-N′-{2-[(3-fluoro-4-methylphenyl)amino]pyridin-3-yl}ethanediamide (C3) (from the preceding step, 8.86 g, ≦16.6 mmol) and ethane-1,2-diol (27 mL) was stirred at 200° C. for 1 hour. After cooling to room temperature, the reaction mixture was diluted with water (100 mL) and aqueous sodium hydroxide solution (1 M, 100 mL), then extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification using silica gel chromatography (Gradient: 5% to 50% ethyl acetate in heptane) was followed by recrystallization from 3:1 toluene/heptane, to afford the product as a solid. Yield: 2.52 g, 8.12 mmol, 49% over three steps. LCMS m/z 311.0 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.50 (dd, J=4.7, 1.5 Hz, 1H), 8.13 (dd, J=8.1, 1.5 Hz, 1H), 7.68 (br s, 1H), 7.37 (dd, J=8.1, 4.7 Hz, 1H), 7.34-7.40 (m, 1H), 7.10-7.15 (m, 2H), 2.83-2.90 (m, 1H), 2.37 (br d, J=2 Hz, 3H), 0.83-0.89 (m, 2H), 0.67-0.72 (m, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification
  8. customwas followed by recrystallization from 3:1 toluene/heptane

Sources & evidence

ORD record
ord-937c8258a00e4f6db7015e691cef42fc
Source dataset
uspto-grants-2015_09
Patent number
US09120788B2

Reaction notes

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