Triethylamine → N-{2-[(2,3-Difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}-3-morpholin-4-ylazetidine-1-sulfonamide

HRID 1025022Notes

Reaction equation

HRID 1025022 reaction equation
[F:1][C:2]1[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][S:5][C:6]1[N:11]=[C:10]([NH:12][S:13]([N:16]2[CH2:19][CH:18](O)[CH2:17]2)(=[O:15])=[O:14])[CH:9]=[C:8]([O:21][CH3:22])[N:7]=1.[CH2:28]([N:30](CC)[CH2:31][CH3:32])[CH3:29].CS(Cl)(=O)=[O:37]>C(Cl)Cl>[F:1][C:2]1[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][S:5][C:6]1[N:11]=[C:10]([NH:12][S:13]([N:16]2[CH2:17][CH:18]([N:30]3[CH2:31][CH2:32][O:37][CH2:29][CH2:28]3)[CH2:19]2)(=[O:15])=[O:14])[CH:9]=[C:8]([O:21][CH3:22])[N:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59558820N-{2-[(2,3-Difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}-3-hydroxyazetidine-1-sulfonamide2×

Product 1

HCID 59558807N-{2-[(2,3-Difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}-3-morpholin-4-ylazetidine-1-sulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of N-{2-[(2,3-difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}-3-hydroxyazetidine-1-sulfonamide (the product from example 109) (0.28 g) in DCM (10 ml) was treated with triethylamine (0.8 ml) and methanesulfonylchloride (0.9 ml) under nitrogen. After heating the mixture at 50° C. for 16 h the reaction mixture was partitioned between DCM and aqueous NaHCO3. The organic extracts were dried (MgSO4), filtered and the solvent evaporated under reduced pressure. To a solution of the resulting residue in MeOH (10 mL) and morpholine (8 ml) K2CO3 (0.19 g) was added and heated at 80° C. for 16 h. The reaction mixture was then partitioned between EtOAc and H2O The organic extracts were washed with brine, dried (MgSO4), filtered and the solvent evaporated under reduced pressure. The residue was purified by reverse phase HPLC (symmetry as the stationary phase and NH4OAc/acetonitrile as the mobile phase) then titurated with Et2O to give the title compound as a white solid. Yield: 15 mg

Workup

  1. customwas partitioned between DCM and aqueous NaHCO3
  2. dry with materialThe organic extracts were dried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent evaporated under reduced pressure
  5. additionTo a solution of the resulting residue in MeOH (10 mL) and morpholine (8 ml) K2CO3 (0.19 g) was added
  6. temperatureheated at 80° C. for 16 h
  7. customThe reaction mixture was then partitioned between EtOAc and H2O The organic extracts
  8. washwere washed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customthe solvent evaporated under reduced pressure
  12. customThe residue was purified by reverse phase HPLC (symmetry as the stationary phase and NH4OAc/acetonitrile as the mobile phase)

Sources & evidence

ORD record
ord-06664051fef24b449b8be82961d0b988
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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