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

HRID 2249981Notes

Reaction equation

HRID 2249981 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 recrystalized 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 recrystalized from 200 mL of a methanol

Sources & evidence

ORD record
ord-159c441e973a46edabf665001779c0e4
Source dataset
uspto-grants-2008_01
Patent number
US07314934B2

Reaction notes

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