Water → 4-Chloro-6-((2,6-difluorophenyl)amino)-2-(methylthio)pyrimidine-5-carbaldehyde

HRID 556528Notes

Reaction equation

HRID 556528 reaction equation
Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([Cl:10])[N:5]=[C:4]([S:11][CH3:12])[N:3]=1.[F:13][C:14]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:15]=1[NH2:16].CCN(CC)CC.O>C(Cl)(Cl)Cl>[Cl:10][C:6]1[C:7]([CH:8]=[O:9])=[C:2]([NH:16][C:15]2[C:14]([F:13])=[CH:20][CH:19]=[CH:18][C:17]=2[F:21])[N:3]=[C:4]([S:11][CH3:12])[N:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 796472,6-DifluoroanilineHCID 46140044,6-Dichloro-2-(methylsulfanyl)pyrimidine-5-carbaldehyde

Product 1

HCID 99447374-Chloro-6-((2,6-difluorophenyl)amino)-2-(methylthio)pyrimidine-5-carbaldehydeYield 76.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 4,6-dichloro-2-methylsulfanyl-pyrimidine-5-carbaldehyde (11.1 g, 50 mmol) in CHCl3 (100 mL) was added 2,6-difluoroaniline (8.07 mL, 75 mmol, 1.5 eq) followed by Et3N (10.43 mL, 75 mmol, 1.5 eq). The reaction mixture turned yellow and was heated to reflux for 24 h, H2O (50 mL) was added and the layers were separated. The organic layer was evaporated and the crude product was recrystallized from 200 mL of a methanol: H2O mixture (2:1) to give 12.03 g (76%) of pure 4-chloro-6-(2,6-difluoro-phenylamino)-2-methylsulfanyl-pyrimidine-5-carbaldehyde. 1H-NMR: δ 2.21 (s, 3H), 6.91 (m, 2H), 7.24 (m, 1H), 10.29 (s, 1H), 10.35 (br s, 1H). LC MS (m/e)=316 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 24 h
  3. customthe layers were separated
  4. customThe organic layer was evaporated
  5. customthe crude product was recrystallized from 200 mL of a methanol

Sources & evidence

ORD record
ord-1b05bf18ad2846bb9cb3763fb9a13035
Source dataset
uspto-grants-2011_11
Patent number
US08058282B2

Reaction notes

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