Pyridine → HCID 59558787, compound

HRID 1024899Notes

Reaction equation

HRID 1024899 reaction equation
[NH2:1][CH2:2][C@@H:3]([CH3:29])[O:4][C:5]1[N:10]=[C:9]([S:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=2[F:20])[N:8]=[C:7]([NH:21][S:22]([N:25]2[CH2:28][CH2:27][CH2:26]2)(=[O:24])=[O:23])[CH:6]=1.N1C=CC=CC=1.[C:36](OC(=O)C)(=[O:38])[CH3:37]>ClCCl>[N:25]1([S:22]([NH:21][C:7]2[N:8]=[C:9]([S:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[F:20])[N:10]=[C:5]([O:4][C@H:3]([CH3:29])[CH2:2][NH:1][C:36](=[O:38])[CH3:37])[CH:6]=2)(=[O:23])=[O:24])[CH2:26][CH2:27][CH2:28]1

Participants

5

Reactant 3

HCID 1049Pyridine3×HCID 7918Acetic Anhydride3×HCID 59558762HCID 59558762, compound

Product 1

HCID 59558787HCID 59558787, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of N-[6-((2)-2-amino-1-methylethoxy)-2-[[(2,3-Difluorophenyl)methyl]thio]pyrimidin-4-yl]azetidine-1-sulfonamide (the title product of Example 42) (0.05 g) in dichloromethane (10 mL) was added pyridine (0.02 mL), followed by acetic anhydride (0.02 mL). The mixture was stirred overnight at room temperature. Pyridine (0.02 mL) and acetic anhydride (0.02 mL) were added and the reaction mixture was stirred for a further 2 h. Pyridine (1.0 mL) and acetic anhydride (0.50 mL) were added and the reaction mixture was stirred for a further 2 h. The reaction mixture was diluted with dichloromethane, washed with aqueous citric acid, H2O, dried (MgSO4), filtered and the solvent evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel using 40% EtOAc in isohexane as eluent. The isolated product was further purified by reverse phase HPLC eluting with acetonitrile/aq. 0.1% ammonium acetate mixtures to give the title compound as a white solid. Yield: 55 mg.

Workup

  1. stirringthe reaction mixture was stirred for a further 2 h
  2. stirringthe reaction mixture was stirred for a further 2 h
  3. washwashed with aqueous citric acid, H2O
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel using 40% EtOAc in isohexane as eluent
  8. customThe isolated product was further purified by reverse phase HPLC
  9. washeluting with acetonitrile/aq

Sources & evidence

ORD record
ord-ce206cede77e42288e86c8cc37f81cb0
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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