2-Methoxyethanol → N-(2-chloro-5-(4-(2-methoxyethoxy)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide

HRID 1963778Notes

Reaction equation

HRID 1963778 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][OH:5].[H-].[Na+].[Cl:8][C:9]1[C:14]([NH:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)(=[O:18])=[O:17])=[CH:13][C:12]([C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[N:32]=[CH:31][CH:30]=[C:29]3Cl)=[CH:11][N:10]=1>CN(C=O)C>[Cl:8][C:9]1[C:14]([NH:15][S:16]([C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)(=[O:17])=[O:18])=[CH:13][C:12]([C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[N:32]=[CH:31][CH:30]=[C:29]3[O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 80192-MethoxyethanolHCID 24758Sodium hydrideHCID 44608916N-(2-chloro-5-(4-chloroquinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide

Product 1

HCID 44609700N-(2-chloro-5-(4-(2-methoxyethoxy)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamideYield 25.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(Some starting materials may be obtained from Aldrich, St. Louis, Mo.) To a solution of 2-methoxyethanol (0.2 mL, 2 mmol) in DMF (10 mL) at 0° C. was added sodium hydride, 60% dispersion in mineral oil (0.09 mL, 2 mmol). After the addition, the ice bath was removed. The reaction mixture was warmed up to rt and continued to stir at rt. After 20 min, N-(2-chloro-5-(4-chloroquinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (0.1 g, 0.2 mmol) was added. It was continued to stir for 20 h. LC/MS showed total conversion. Reaction was quenched with water. The resulting mixture was partitioned between EtOAc/water. The organic layer was washed with water, brine, dried over MgSO4 and concentrated. The crude product was purified using SiO2 (12 g) chromatography with hexanes:acetone=80%:20% as the solvent system to afford the desired product as light yellow solid (25 mg). A peak at 28 min was collected. The solvent was removed in vacuo to afford the desired product as light yellow solid (80.0 mg). MS (ESI pos. ion) m/z: calc'd for C23H19ClFN3O4S: 487.1; found: 488.4 (M+1). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.53 (s, 3 H) 3.90-4.00 (m, 2 H) 4.35-4.49 (m, 2 H) 6.84 (d, J=5.26 Hz, 1 H) 7.19 (t, J=8.55 Hz, 2 H) 7.88 (ddd, J=8.62, 4.17, 3.87 Hz, 3 H) 8.17 (d, J=8.77 Hz, 1 H) 8.33 (d, J=2.34 Hz, 1 H) 8.43 (d, J=1.90 Hz, 1 H) 8.50 (d, J=2.34 Hz, 1 H) 8.81 (d, J=5.26 Hz, 1 H).

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. stirringto stir for 20 h
  4. customReaction
  5. customwas quenched with water
  6. customThe resulting mixture was partitioned between EtOAc/water
  7. washThe organic layer was washed with water, brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe crude product was purified

Sources & evidence

ORD record
ord-9a0d84e39b354a309ac99cae86682d3e
Source dataset
uspto-grants-2013_04
Patent number
US08415376B2

Reaction notes

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