Water → 5-(azetidin-1-ylcarbonyl)-N-{2-[(2,3-difluorobenzyl)thio]-6-[(1R)-2-hydroxy-1-methylethoxy]pyrimidin-4-yl}furan-2-sulfonamide

HRID 1024914Notes

Reaction equation

HRID 1024914 reaction equation
[N:1]1([C:5]([C:7]2[O:11][C:10]([S:12]([NH:15][C:16]3[CH:21]=[C:20]([O:22][C@H:23]([CH3:45])[CH2:24][O:25]C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:19]=[C:18]([S:46][CH2:47][C:48]4[CH:53]=[CH:52][CH:51]=[C:50]([F:54])[C:49]=4[F:55])[N:17]=3)(=[O:14])=[O:13])=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(OC)C=CC=CC=1.O>CO>[N:1]1([C:5]([C:7]2[O:11][C:10]([S:12]([NH:15][C:16]3[CH:21]=[C:20]([O:22][C@H:23]([CH3:45])[CH2:24][OH:25])[N:19]=[C:18]([S:46][CH2:47][C:48]4[CH:53]=[CH:52][CH:51]=[C:50]([F:54])[C:49]=4[F:55])[N:17]=3)(=[O:14])=[O:13])=[CH:9][CH:8]=2)=[O:6])[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 7519AnisoleHCID 521998p-Toluenesulfonic acid monohydrateHCID 536283645-(azetidin-1-ylcarbonyl)-N-{2-[(2,3-difluorobenzyl)thio]-6-[(1R)-1-methyl-2-(triphenylmethyloxy)ethoxy]pyrimidin-4-yl}furan-2-sulfonamide

Product 1

HCID 115701665-(azetidin-1-ylcarbonyl)-N-{2-[(2,3-difluorobenzyl)thio]-6-[(1R)-2-hydroxy-1-methylethoxy]pyrimidin-4-yl}furan-2-sulfonamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-(azetidin-1-ylcarbonyl)-N-{2-[(2,3-difluorobenzyl)thio]-6-[(1R)-1-methyl-2-(triphenylmethyloxy)ethoxy]pyrimidin-4-yl}furan-2-sulfonamide (the product of step iv) (0.24 g) in methanol (5 mL) was added para-toluenesulfonic acid hydrate (58 mg) and anisole (0.34 mL). After stirring at room temperature for 2d, H2O (5 mL) was added and the mixture extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (10 mL), dried (MgSO4), filtered and evaporated to dryness in vacuo. The resulting crude solid was purified by reverse phase HPLC (50% to 5% gradient of 0.1% aqueous ammonium acetate in acetonitrile as eluent) to give the title compound as a white solid. Yield: 10 mg.

Workup

  1. additionwas added
  2. extractionthe mixture extracted with EtOAc (3×10 mL)
  3. washThe combined organic layers were washed with brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated to dryness in vacuo
  7. customThe resulting crude solid was purified by reverse phase HPLC (50% to 5% gradient of 0.1% aqueous ammonium acetate in acetonitrile as eluent)

Sources & evidence

ORD record
ord-ba8652398af04c239abd2eb4121a3c68
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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