Acetyl chloride → N-[3,5-Difluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]acetamide

HRID 2192148Notes

Reaction equation

HRID 2192148 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:19])[C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:16][CH:17]=[CH:18][C:11]=12)[NH2:5].C(N(CC)CC)C.[C:27](Cl)(=[O:29])[CH3:28].C(=O)(O)[O-].[Na+].C[O-].[Na+]>ClCCl>[F:19][C:7]1[CH:6]=[C:4]([NH:5][C:27](=[O:29])[CH3:28])[CH:3]=[C:2]([F:1])[C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:16][CH:17]=[CH:18][C:11]=12

Participants

7

Reactant 5

HCID 6367Acetyl chloride2×HCID 8471Triethylamine2×HCID 516892Sodium BicarbonateHCID 10942334Sodium MethoxideHCID 179792873,5-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline

Product 1

HCID 59740995N-[3,5-Difluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1.60 g (6.14 mmol) of 3,5-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline are suspended in 45 ml of dichloromethane and cooled to 0° C. 2.57 ml (18.4 mmol) of triethylamine and 0.87 ml (12.3 mmol) of acetyl chloride are added dropwise, and stirring at 0° C. is continued for 2.5 hours. A further 0.86 ml (6.14 mmol) of triethylamine and 0.44 ml (6.14 mmol) of acetyl chloride are added, and the mixture is allowed to react for another hour. Saturated sodium bicarbonate solution is then added, and the mixture is stirred at RT for 10 min. The mixture is extracted twice with dichloromethane. The combined organic phases are dried over magnesium sulfate and the solvent is removed under reduced pressure. The crude product is taken up in 45 ml of ethanol. 1.14 ml (6.14 mmol) of 5.4M sodium methoxide solution are added, and the mixture is stirred at RT for 30 min. The mixture is concentrated and the product is purified by chromatography on silica gel (mobile phase: dichloromethane/methanol (7N ammonia) 100:1 to 100:5).

Workup

  1. customto react for another hour
  2. stirringthe mixture is stirred at RT for 10 min
  3. extractionThe mixture is extracted twice with dichloromethane
  4. dry with materialThe combined organic phases are dried over magnesium sulfate
  5. customthe solvent is removed under reduced pressure
  6. stirringthe mixture is stirred at RT for 30 min
  7. concentrationThe mixture is concentrated
  8. customthe product is purified by chromatography on silica gel (mobile phase: dichloromethane/methanol (7N ammonia) 100:1 to 100:5)

Sources & evidence

ORD record
ord-da2ae1a2f3df4b2da8e45e40a0b65af0
Source dataset
uspto-grants-2012_12
Patent number
US08329716B2

Reaction notes

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