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

HRID 1958884Notes

Reaction equation

HRID 1958884 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][S:10][C:11]1[N:16]=[C:15]([NH:17][S:18]([N:21]2[CH2:24][CH2:23][CH2:22]2)(=[O:20])=[O:19])[CH:14]=[C:13]([O:25][CH:26]2[CH2:31][O:30]C(C3C=CC=CC=3)[O:28][CH2:27]2)[N:12]=1.O.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>CO>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][S:10][C:11]1[N:16]=[C:15]([NH:17][S:18]([N:21]2[CH2:24][CH2:23][CH2:22]2)(=[O:20])=[O:19])[CH:14]=[C:13]([O:25][CH:26]([CH2:27][OH:28])[CH2:31][OH:30])[N:12]=1

Participants

5

Reactant 3

HCID 962WaterHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 53628338N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-4-pyrimidinyl]-1-azetidinesulfonamide

Product 1

HCID 11698344N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[2-hydroxy-1-(hydroxymethyl)ethoxy]-4-pyrimidinyl]-1-azetidinesulfonamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-4-pyrimidinyl]-1-azetidinesulfonamide (the product of step iv) (220 mg) in methanol (5 ml)/water (0.1 ml) was added pyridinium p-toluenesulfonate (20 mg) and the mixture was stirred at ambient temperature for 1.5 hour, then at reflux for 20 hour. The reaction mixture was evaporated, suspended in water and extracted with ethyl acetate (×2). The combined organic layers were dried with magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography on silica gel using a 98:2 mixture of methylene chloride and methanol as eluent to give the title compound as a white solid. Yield: 120 mg

Workup

  1. temperatureat reflux for 20 hour
  2. customThe reaction mixture was evaporated
  3. extractionextracted with ethyl acetate (×2)
  4. dry with materialThe combined organic layers were dried with magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography on silica gel using
  8. additiona 98:2 mixture of methylene chloride and methanol as eluent

Sources & evidence

ORD record
ord-53294430e15e41f18fa6987765e22a20
Source dataset
uspto-grants-2013_04
Patent number
US08410123B2

Reaction notes

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