Sodium Iodide → 5-(2-{4-[5-(4-Fluoro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperazin-1-yl}-ethyl)-2-methoxy-benzenesulfonamide

HRID 2288998노트

반응식

HRID 2288998 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:19][O:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:4][CH:3]=1.Cl[CH2:27][CH2:28][C:29]1[CH:30]=[CH:31][C:32]([O:39][CH3:40])=[C:33]([S:35]([NH2:38])(=[O:37])=[O:36])[CH:34]=1.[I-].[Na+].C(N(C(C)C)CC)(C)C>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([N:13]3[CH2:18][CH2:17][N:16]([CH2:27][CH2:28][C:29]4[CH:30]=[CH:31][C:32]([O:39][CH3:40])=[C:33]([S:35]([NH2:38])(=[O:36])=[O:37])[CH:34]=4)[CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:19][O:20][CH2:21][C:22]([F:25])([F:23])[F:24])=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 187004001-[5-(4-Fluoro-Phenyl)-4-(2,2,2-Trifluoro-Ethoxymethyl)-Oxazol-2-yl]-PiperazineHCID 187004435-(2-Chloroethyl)-2-methoxy-benzenesulfonamide

생성물 1

HCID 187003995-(2-{4-[5-(4-Fluoro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperazin-1-yl}-ethyl)-2-methoxy-benzenesulfonamide수율 58.2%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

A solution of 1-[5-(4-fluoro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperazine (0.15 g; 0.42 mmol) in dry dioxane (5 ml) is treated with 5-(2-chloroethyl)-2-methoxy-benzenesulfonamide (0.25 g; 1.0 mmol), sodium iodide (0.15 g; 1.0 mmol) and diisopropylethylamine (0.36 ml; 2.09 mmol) and heated to 100 C. for 16 hours. The reaction mixture is partitioned between ethyl acetate (40 ml) and dilute sodium bicarbonate (20 ml). The aqueous phase is extracted with ethyl acetate (20 ml). The combined organic phases are washed with saturated brine (10 ml), dried over sodium sulfate and concentrated to dryness. Purification by radial chromatography on silica gel using a methanol-ethyl acetate gradient (1%-20%) is followed by a second chromatography using a methanol-dichloromethane gradient (1%-5%). Crystallization from ethyl acetate/hexane affords the product as a white solid (0.14 g; 56%). HNMR (CDCL3): 7.81 (d, 1H, J=2.4 Hz), 7.54 (m, 2H), 7.42 (dd, 1H, J=8.7, 2.0 Hz), 7.14 (t, 2H, J=8.8 Hz), 7.02 (d, 1H, J=8.7 Hz), 5.16 (s, 2H), 4.04 (s, 3H), 4.01 (qt, 2H, J=8.8 Hz), 3.62 (m, 4H), 2.85 (m, 2H), 2.66 (m, 6H).

후처리

  1. temperatureheated to 100 C
  2. customThe reaction mixture is partitioned between ethyl acetate (40 ml) and dilute sodium bicarbonate (20 ml)
  3. extractionThe aqueous phase is extracted with ethyl acetate (20 ml)
  4. washThe combined organic phases are washed with saturated brine (10 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customPurification by radial chromatography on silica gel using a methanol-ethyl acetate gradient (1%-20%)
  8. customCrystallization from ethyl acetate/hexane

출처 및 근거

ORD 기록
ord-8ae46205882447d2a7fd3c2e38b26233
출처 데이터셋
uspto-grants-2000_07
특허 번호
US06090825

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