p-Toluenesulfonic acid → N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-2-hydroxy-1-methylethoxy]-4-pyrimidinyl]-4-pyridinesulfonamide

HRID 2388743Notes

Reaction equation

HRID 2388743 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]([C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[CH:14]=[C:13]([O:27][C@H:28]([CH3:50])[CH2:29][O:30]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:12]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(OC)C=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]([C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)(=[O:19])=[O:20])[CH:14]=[C:13]([O:27][C@H:28]([CH3:50])[CH2:29][OH:30])[N:12]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 7519AnisoleHCID 53628344N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-4-pyrimidinyl]-4-pyridinesulfonamide

Product 1

HCID 11540012N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-2-hydroxy-1-methylethoxy]-4-pyrimidinyl]-4-pyridinesulfonamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-4-pyrimidinyl]-4-pyridinesulfonamide (the product from step iv). (100 mg) in MeOH (10 mL) was added p-toluenesulfonic acid (31 mg) and anisole (0.15 g). The reaction was then stirred at room temperature for 18 h. The reaction was partitioned between EtOAc (100 mL) and H2O (100 mL). The aqueous layer was then further extracted with EtOAc (2×100 mL). The combined organic layers were dried (MgSO4), filtered and evaporated. The residue was purified by reverse phase HPLC using a TFA (0.2%)/MeCN to give the title compound as a white solid. Yield: 50 mg.

Workup

  1. customThe reaction was partitioned between EtOAc (100 mL) and H2O (100 mL)
  2. extractionThe aqueous layer was then further extracted with EtOAc (2×100 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-137b4ea0aec94e9fba93befe647a88e8
Source dataset
uspto-grants-2012_09
Patent number
US08269002B2

Reaction notes

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