Methanesulfonyl chloride → HCID 59843032, compound

HRID 1878785Notes

Reaction equation

HRID 1878785 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[CH:12][C:13](=[O:31])[N:14]([CH2:16][CH2:17][O:18][C:19]3[C:28]4[C:23](=[CH:24][C:25]([O:29][CH3:30])=[CH:26][CH:27]=4)[N:22]=[CH:21][CH:20]=3)[N:15]=2)[CH:5]=[CH:6][C:7]=1[CH2:8]O.CS(Cl)(=O)=O.[N-:37]=[N+:38]=[N-:39].[Na+]>C(Cl)Cl.O>[N:37]([CH2:8][C:7]1[CH:6]=[CH:5][C:4]([C:10]2[CH:11]=[CH:12][C:13](=[O:31])[N:14]([CH2:16][CH2:17][O:18][C:19]3[C:28]4[C:23](=[CH:24][C:25]([O:29][CH3:30])=[CH:26][CH:27]=4)[N:22]=[CH:21][CH:20]=3)[N:15]=2)=[CH:3][C:2]=1[Cl:1])=[N+:38]=[N-:39]

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 59843010HCID 59843010, compound

Product 1

HCID 59843032HCID 59843032, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a stirring solution of 6-(3-chloro-4-(hydroxymethyl)phenyl)-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one (1060 mg, 2421 μmol) and TEA (337 μL, 2421 μmol) in DCM (10 mL) at 0° C. under nitrogen was added methanesulfonyl chloride (187 μL, 2421 μmol) in DCM (1 mL). After 3 hours, the mixture was partitioned between DCM (25 mL) and 5% NaHCO3 (25 mL). The aqueous layer was further extracted with DCM (2×10 mL). The combined organics were dried over MgSO4, then concentrated to a solid. Solid was then dissolved in DMF (5 mL) and sodium azide (787 mg, 12104 μmol) in water (5 mL) was then added. The biphasic solution was then heated to 60° C. overnight. The reaction was then partitioned between DCM (25 mL) and 5% NaHCO3 (25 mL). The aqueous layer was then further extracted with DCM (2×10 mL). The combined organics were then dried over MgSO4, concentrated, and purified on silica (40 g) eluting with 1 to 4% of MeOH/DCM. MS (ESI pos. ion) m/z: 463 (MH+); calc'd for C23H19ClN6O3: 462.

Workup

  1. customthe mixture was partitioned between DCM (25 mL) and 5% NaHCO3 (25 mL)
  2. extractionThe aqueous layer was further extracted with DCM (2×10 mL)
  3. dry with materialThe combined organics were dried over MgSO4
  4. concentrationconcentrated to a solid
  5. dissolutionSolid was then dissolved in DMF (5 mL)
  6. customThe reaction was then partitioned between DCM (25 mL) and 5% NaHCO3 (25 mL)
  7. extractionThe aqueous layer was then further extracted with DCM (2×10 mL)
  8. dry with materialThe combined organics were then dried over MgSO4
  9. concentrationconcentrated
  10. custompurified on silica (40 g)
  11. washeluting with 1 to 4% of MeOH/DCM

Sources & evidence

ORD record
ord-708fd4545bba492287ad2a446ebf001f
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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