Sodium Iodide → 5-(2-{4-[5-(4-Fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-hydroxy-benzenesulfonamide

HRID 2288996노트

반응식

HRID 2288996 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:19][OH:20])=[CH:4][CH:3]=1.Cl[CH2:22][CH2:23][C:24]1[CH:25]=[CH:26][C:27]([OH:34])=[C:28]([S:30]([NH2:33])(=[O:32])=[O:31])[CH:29]=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]([CH:13]3[CH2:14][CH2:15][N:16]([CH2:22][CH2:23][C:24]4[CH:25]=[CH:26][C:27]([OH:34])=[C:28]([S:30]([NH2:33])(=[O:31])=[O:32])[CH:29]=4)[CH2:17][CH2:18]3)=[N:10][C:9]=2[CH2:19][OH:20])=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 187004285-(2-Chloroethyl)-2-hydroxy-benzenesulfonamideHCID 18700441[5-(4-Fluoro-Phenyl)-2-Piperidin-4-yl-Oxazol-4-yl]Methanol

생성물 1

HCID 187004715-(2-{4-[5-(4-Fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-hydroxy-benzenesulfonamide수율 16.1%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

A solution of [5-(4-fluoro-phenyl)-2-piperidin-4-yl-oxazol-4-yl]methanol (0.20 g; 0.72 mmol) in dry dioxane (6 ml) is treated with 5-(2-chloroethyl)-2-hydroxy-benzenesulfonamide (0.36 g; 1.45 mmol), sodium iodide (0.22 g; 1.45 mmol) and diisopropylethylamine (0.50 ml; 2.88 mmol) and heated to 100 C. for 16 hours. The reaction is cooled and partitioned between ethyl acetate (30 ml) and water (10 ml). The aqueous phase is washed with ethyl acetate (2×15 ml), dried over sodium sulfate and concentrated to dryness. Purification by radial chromatography using a methanol/ethyl acetate gradient (5%-40%) is followed by a second chromatography using a methanol/dichloromethane gradient (5%-30%). Crystallization from methanol/ethyl acetate afforded the product as a white solid (0.055 g; 16%). HNMR (CD3OD): 7.75 (m, 2H), 7.64 (d, 1H, J=2.1 Hz), 7.31 (dd, 1H, J=8.4; 2.1 Hz), 7.23 (t, 2H, J=8.8 Hz), 6.92 (d, 1H, J=8.4 Hz), 4.63 (s, 2H), 3.12 (m, 2H), 2.96 (m, 1H), 2.82 (m, 2H), 2.66 (m, 2H), 2.34 (m, 2H), 2.17 (m, 2H), 1.99 (m, 2H). Mass spectrum: m/e calculated (MH+)=476.6; observed (MH+)=476.2.

후처리

  1. temperatureheated to 100 C
  2. temperatureThe reaction is cooled
  3. custompartitioned between ethyl acetate (30 ml) and water (10 ml)
  4. washThe aqueous phase is washed with ethyl acetate (2×15 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customPurification by radial chromatography
  8. customCrystallization from methanol/ethyl acetate

출처 및 근거

ORD 기록
ord-f8940c635d42446c953263185b91254f
출처 데이터셋
uspto-grants-2000_07
특허 번호
US06090825

반응 노트

불러오는 중…