Chloroacetaldehyde → Methyl 7-(4-bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylate

HRID 494702Notes

Reaction equation

HRID 494702 reaction equation
Cl[CH2:2][CH:3]=O.[CH3:5][O:6][C:7](=[O:25])[C:8]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[Cl:22])=[C:12]([Cl:23])[C:11]([NH2:24])=[N:10][CH:9]=1>CN(C=O)C.O>[CH3:5][O:6][C:7]([C:8]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[Cl:22])=[C:12]([Cl:23])[C:11]2[N:10]([CH:2]=[CH:3][N:24]=2)[CH:9]=1)=[O:25]

Participants

5

Reactant 2

HCID 33ChloroacetaldehydeHCID 59519500Methyl 6-amino-4-(4-bromo-2-chlorophenylamino)-5-chloronicotinate

Product 1

HCID 58886653Methyl 7-(4-bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Chloroacetaldehyde (50% aqueous solution, 0.70 mL, 5.7 mmol) was added to a suspension of 6-amino-4-(4-bromo-2-chlorophenylamino)-5-chloronicotinic acid methyl ester (28) in DMF (7 mL) contained in a sealed tube. The reaction mixture was heated at 80° C. for four hours and then allowed to cool to room temperature and stir overnight. The dark brown solution was diluted with water (70 mL) the resulting light brown precipitate was collected by filtration and washed with water. The solids were dissolved into THF. Two volumes of ethyl acetate were added and the organic solution washed with brine, dried over NaSO4, filtered, and concentrated in vacuo to provide a brown solid. The aqueous filtrate was extracted with ethyl acetate and the organic extracts were dried over NaSO4, filtered, and concentrated in vacuo. This material was combined with the previously isolated brown solid and the combined material subjected to column chromatography (dichloromethane, followed by 20:1 dichloromethane/methanol). The desired product (29) was isolated as a light yellow solid (0.752 g, 64%). MS (APCI+) m/z 414, 416, 418 (M+; Cl, Br pattern) detected.

Workup

  1. customcontained in a sealed tube
  2. temperatureto cool to room temperature
  3. filtrationwas collected by filtration
  4. washwashed with water
  5. dissolutionThe solids were dissolved into THF
  6. additionTwo volumes of ethyl acetate were added
  7. washthe organic solution washed with brine
  8. dry with materialdried over NaSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto provide a brown solid
  12. extractionThe aqueous filtrate was extracted with ethyl acetate
  13. dry with materialthe organic extracts were dried over NaSO4
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-55c88b07677a41cf903a05c990e58087
Source dataset
uspto-grants-2009_05
Patent number
US07538120B2

Reaction notes

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