Dimethylformamide → 4-[2-(3-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxy)-4-phenyl-5-oxazolyl]benzenesulfonamide

HRID 890872Notes

Reaction equation

HRID 890872 reaction equation
Cl[C:2]1[O:3][C:4]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:6]=1.[CH3:23]N(C=O)C.C(=O)([O-])[O-].[K+].[K+].[OH:34][C:35]1[CH:36]=[C:37]([CH:41]2[CH2:46][CH:45]([O:47][CH3:48])C[CH2:43][O:42]2)[CH:38]=[CH:39][CH:40]=1>C(OCC)(=O)C>[CH3:43][O:42][C:41]1([C:37]2[CH:36]=[C:35]([CH:40]=[CH:39][CH:38]=2)[O:34][C:2]2[O:3][C:4]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)=[C:5]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[N:6]=2)[CH2:46][CH2:45][O:47][CH2:48][CH2:23]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 222460994-(2-Chloro-4-phenyl-5-oxazolyl)benzenesulfonamideHCID 22246254(3-hydroxyphenyl)-4-methoxy-3,4,5,6-tetrahydro-2H-pyran

Product 1

HCID 129861274-[2-(3-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxy)-4-phenyl-5-oxazolyl]benzenesulfonamideYield 44%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-(2-Chloro-4-phenyl-5-oxazolyl]benzenesulfonamide from Example 4, Step 3, (0.6 g, 1.8 mmol), DMF (20 mL), potassium carbonate (0.5 g, 3.6 mmol), and 4 (3-hydroxyphenyl)-4-methoxy-3,4,5,6-tetrahydro-2H-pyran (0.37 g, 1.8 mmol) [prepared as described by G. C. Crawley, et al, J. Med. Chem., 35, 2600–2609 (1992)] were stirred at room temperature for 16.0 hours. The solution was diluted with ethyl acetate (100 mL), washed with 1N HCl, brine and water, dried over MgSO4 and concentrated. The residue was dissolved in ethyl acetate/hexanes (1:1) and filtered through silica. The eluant was concentrated and the residue recrystallized from ethyl acetate/hexanes to give 4-[2-(3-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxy)-4-phenyl-5-oxazolyl]benzenesulfonamide as a white solid (0.4 g, 44%): mp 145–147° C. 1H NMR (CDCl3) 300 MHz δ 7.88 (d, J=8.9 Hz, 2H) 7.70 (d, J=8.9 Hz, 2H) 7.6 (m, 2H) 7.36–7.5 (m, 6H) 7.0–7.1 (dt, J=6.4 Hz and J=2.2 Hz, 1H) 4.85 (bs, 2H) 3.7 (m, 4H) 3.05 (s, 3H) 2.0 (m, 4H). Anal. Calc'd. for C27H26N2O6S: C, 64.02; H, 5.17; N, 5.53. Found: C, 63.94; H, 5.17; N, 5.55.

Workup

  1. washwashed with 1N HCl, brine and water
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in ethyl acetate/hexanes (1:1)
  5. filtrationfiltered through silica
  6. concentrationThe eluant was concentrated
  7. customthe residue recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-7ffe14c148084c608e2abdde8f6d460f
Source dataset
uspto-grants-2006_02
Patent number
US06998415B2

Reaction notes

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