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

HRID 1839552Notes

Reaction equation

HRID 1839552 reaction equation
Cl[CH2:2][C:3]1[O:4][C:5]([C:14]2[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][CH:15]=2)=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.[F:35][C:36]1[CH:37]=[C:38]([OH:50])[CH:39]=[C:40]([C:42]2([O:48][CH3:49])[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)[CH:41]=1>O>[F:35][C:36]1[CH:37]=[C:38]([CH:39]=[C:40]([C:42]2([O:48][CH3:49])[CH2:43][CH2:44][O:45][CH2:46][CH2:47]2)[CH:41]=1)[O:50][CH2:2][C:3]1[O:4][C:5]([C:14]2[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][CH:15]=2)=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 117362763-Fluoro-5-(4-methoxytetrahydro-2H-pyran-4-yl)phenolHCID 222463454-[2-Chloromethyl-4-phenyloxazol-5-yl]benzenesulfonamide

Product 1

HCID 129861294-[2-[[3-Fluoro-5-(3,4,5,6-tetrahydro-4-methoxy-pyran-4-yl)phenoxy]methyl]-4-phenyl-oxazol-5-yl]benzenesulfonamideYield 40%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-[2-chloromethyl-4-phenyloxazol-5-yl]benzenesulfonamide (Step 3) (0.5 g, 1.4 mmol), potassium carbonate (0.4 g, 2.8 mmol), dimethylformamide (20 mL), and 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenol [prepared as described in J. Med Chem., 35, 2600-2609 (1992)] (0.3 g, 1.4 mmol) was stirred at room temperature for 16 h. Water (20 mL) was added, and the mixture was extracted with ethyl acetate (4×30 mL). The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated. The resulting crude product was purified by flash column chromatography on silica gel eluting with 50% ethyl acetate in hexanes to give 0.3 g (40%) of 4-[2-[[3-fluoro-5-(3,4,5,6-tetrahydro-4-methoxy-pyran-4-yl)phenoxy]methyl]-4-phenyl-oxazol-5-yl]benzenesulfonamide as a sticky white solid: m.p. 70-80° C. 1H NMR (CDCl3/300 MHz) δ 7.92 (d, 2H, J=8.9 Hz), 7.77 (d, 2H, J=8.9 Hz) , 7.62 (m, 2H) , 7.43 (m, 3H) , 6.94 (s, 1H), 6.78 (m, 2H) 5.24 (s, 2H) , 4.82 (bs, 2H), 3.82 (m, 4H), 3.00 (s, 3H), 1.95 (m, 4H). Anal. calcd for C28H27FN2O6S: C, 62.44; H, 5.05; N, 5.20. Found: C, 62.50; H, 5.11; N, 5.24.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (4×30 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe resulting crude product was purified by flash column chromatography on silica gel eluting with 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-00abcb9506f34176b67a88e890dc6a98
Source dataset
uspto-grants-2004_01
Patent number
US06677364B2

Reaction notes

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