4-Fluoroaniline → 4-Chloro-2-methylsulfanylpyrimidine-5-carboxylic acid (4-fluorophenyl)amide

HRID 348491Notes

Reaction equation

HRID 348491 reaction equation
[Cl:1][C:2]1[C:7]([C:8](Cl)=[O:9])=[CH:6][N:5]=[C:4]([S:11][CH3:12])[N:3]=1.[F:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=1.CCN(C(C)C)C(C)C>ClCCl>[F:13][C:14]1[CH:20]=[CH:19][C:17]([NH:18][C:8]([C:7]2[C:2]([Cl:1])=[N:3][C:4]([S:11][CH3:12])=[N:5][CH:6]=2)=[O:9])=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 97314-FluoroanilineHCID 81531DiisopropylethylamineHCID 189690784-Chloro-2-(methylsulfanyl)pyrimidine-5-carbonyl chloride

Product 1

HCID 188588054-Chloro-2-methylsulfanylpyrimidine-5-carboxylic acid (4-fluorophenyl)amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 4-chloro-2-methylsulfanylpyrimidine-5-carbonyl chloride prepared above (113 mg, 0.54 mmol) in dichloromethane was added 4-fluoroaniline (56 μL, 0.59 mmol). This was followed by the dropwise addition of DIPEA. The mixture was stirred for 15 min, the mixture was diluted with dichloromethane, washed with water and saturated aqueous sodium bicarbonate and was dried over sodium sulfate. Filtration and concentration afforded a residue that was purified by trituration from ethyl acetate with hexanes. The resulting off-white solid (122 mg, 0.41 mmol, 76%) was sufficiently pure to use without further purification. 1H NMR (300 MHz, DMSO-d6) δ 10.7 (s, 1H), 8.86 (s, 1H), 7.69 (m, 2H), 7.23 (m, 2H), 2.56 (s, 3H); MS (EI) m/z 296.2 (M−H)−.

Workup

  1. washwashed with water and saturated aqueous sodium bicarbonate
  2. dry with materialwas dried over sodium sulfate
  3. filtrationFiltration and concentration
  4. customafforded a residue that
  5. customwas purified by trituration from ethyl acetate with hexanes
  6. customto use without further purification

Sources & evidence

ORD record
ord-1bacc08fb4674fb596de52e47b564ec9
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Reaction notes

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