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 890877노트

반응식

HRID 890877 반응식
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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 962Water용매

실험 절차

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.

후처리

  1. extractionthe mixture was extracted with ethyl acetate (4×30 mL) The combined organic layers
  2. washwere 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

출처 및 근거

ORD 기록
ord-ade8ea54b2d74d738dc95452b0785d9e
출처 데이터셋
uspto-grants-2006_02
특허 번호
US06998415B2

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