N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[2-hydroxy-1-(hydroxymethyl)ethoxy]-4-pyrimidinyl]-1-azetidinesulfonamide → 4-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-(1,1-dimethylethoxy)-pyrimidine

HRID 2388753Notes

Reaction equation

HRID 2388753 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=2[F:18])[N:3]=1.FC1C(F)=CC=CC=1CSC1N=C(NS(N2CCC2)(=O)=O)C=C(OC(CO)CO)N=1.[CH3:49][C:50]([CH3:53])([O-:52])[CH3:51].[K+]>C1COCC1.O>[Cl:8][C:6]1[CH:7]=[C:2]([O:52][C:50]([CH3:53])([CH3:51])[CH3:49])[N:3]=[C:4]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=2[F:18])[N:5]=1

Participants

6

Reactant 3

HCID 11698344N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[2-hydroxy-1-(hydroxymethyl)ethoxy]-4-pyrimidinyl]-1-azetidinesulfonamideHCID 23665647Potassium tert-butoxide2×HCID 859280374,6-Dichloro-2-((2,3-difluorobenzyl)thio)pyrimidine

Product 1

HCID 866198744-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-(1,1-dimethylethoxy)-pyrimidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4,6-Dichloro-2-[(2,3-difluorobenzyl)thio]pyrimidine (the product of example 1 step (2 g) in THF (20 mL) was added potassium tert-butoxide (0.8 g) and the reaction mixture was stirred at ambient temperature for 20 h. Further potassium tert-butoxide (0.8 g) was added and the reaction mixture was stirred at ambient temperature for 411. The mixture was diluted with H2O and extracted with EtOAc (×3). The combined organic layers were washed with H2O and dried (MgSO4), filtered and evaporated. The resulting oil was purified by column chromatography on silica gel using MeOH/DCM (99:1 to 98:2 gradient) as eluent to give the subtitle compound as a clear, colourless oil. Yield: 0.68 g

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 411
  2. extractionextracted with EtOAc (×3)
  3. washThe combined organic layers were washed with H2O
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe resulting oil was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-7f0610193bf548f09a2cc4d9482dbe09
Source dataset
uspto-grants-2012_09
Patent number
US08269002B2

Reaction notes

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