Acetic Anhydride → N-Acetyl-N-[4-(4-cyano-3,5-difluorophenyl)-6-(ethylamino)-2-pyrimidinyl]acetamide

HRID 2367209Notes

Reaction equation

HRID 2367209 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[C:14]([F:16])[C:11]([CH:12]=O)=[C:10]([F:17])[CH:9]=2)[CH:5]=[C:4]([NH:18][CH2:19][CH3:20])[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl.[NH2:28]O.C(O[C:34](=[O:36])[CH3:35])(=O)C.[CH3:37][CH2:38][OH:39].O>>[C:38]([N:1]([C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[C:14]([F:16])[C:11]([C:12]#[N:28])=[C:10]([F:17])[CH:9]=2)[CH:5]=[C:4]([NH:18][CH2:19][CH3:20])[N:3]=1)[C:34](=[O:36])[CH3:35])(=[O:39])[CH3:37]

Participants

6

Reactant 5

HCID 7918Acetic AnhydrideHCID 10340Sodium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 19096565Water ethanolHCID 58504843HCID 58504843, compound

Product 1

HCID 58504520N-Acetyl-N-[4-(4-cyano-3,5-difluorophenyl)-6-(ethylamino)-2-pyrimidinyl]acetamideYield 10%

Procedure

To a solution of 4-[2-amino-6-(ethylamino)-4-pyrimidinyl]-2,6-difluorobenzaldehyde (1.57 g, 5.64 mmol) in EtOH/water were added sodium carbonate (0.66 g, 6.21 mmol) and hydroxylamine hydrochloride (0.431 g, 6.21 mmol). The resulting mixture was refluxed until the starting material was consumed. The reaction mixture was concentrated to a dark solid. The solid was washed with water and the aqueous washings were extracted with EtOAc. The solid and EtOAc extractions were combined to afford a dark solid. The solid was treated with acetic anhydride (excess) and stirred at 100° C. until the oxime was converted to the nitrile (˜5 days). The reaction mixture was concentrated and co-evaporated with EtOH. The resulting dark solid was triturated with CH3OH to afford the title compound (0.2 g, 10%) as a dark brown solid. LC-MS (ES) m/z=360 [M+H]+.

Workup

  1. temperatureThe resulting mixture was refluxed until the starting material
  2. customwas consumed
  3. concentrationThe reaction mixture was concentrated to a dark solid
  4. washThe solid was washed with water
  5. extractionthe aqueous washings were extracted with EtOAc
  6. extractionThe solid and EtOAc extractions
  7. customto afford a dark solid
  8. concentrationThe reaction mixture was concentrated and co-evaporated with EtOH
  9. customThe resulting dark solid was triturated with CH3OH

Sources & evidence

ORD record
ord-94855b1bfed24521b4dd99aa3eed8f50
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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