Sodium hydride → (RS)-1-{2-[5,6-Difluoro-1-(2-methoxy-ethyl)-1H-benzoimidazol-2-ylmethyl]-piperidin-1-yl}-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone

HRID 2077334ノート

反応式

HRID 2077334 の反応式
[F:1][C:2]1[C:32]([F:33])=[CH:31][C:5]2[NH:6][C:7]([CH2:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][N:11]3[C:16]([C:18]3[N:19]=[C:20]([CH3:30])[S:21][C:22]=3[C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[O:17])=[N:8][C:4]=2[CH:3]=1.[H-].[Na+].Br[CH2:37][CH2:38][O:39][CH3:40].C(N(CC)C(C)C)(C)C>CN(C=O)C.[I-].[K+]>[F:1][C:2]1[C:32]([F:33])=[CH:31][C:5]2[N:6]([CH2:37][CH2:38][O:39][CH3:40])[C:7]([CH2:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][N:11]3[C:16]([C:18]3[N:19]=[C:20]([CH3:30])[S:21][C:22]=3[C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[O:17])=[N:8][C:4]=2[CH:3]=1

参加物

7

反応物 4

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 81531DiisopropylethylamineHCID 17973672(RS)-1-[2-(5,6-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone

生成物 1

HCID 66967856(RS)-1-{2-[5,6-Difluoro-1-(2-methoxy-ethyl)-1H-benzoimidazol-2-ylmethyl]-piperidin-1-yl}-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone収率 65%

試薬・触媒・溶媒 2

HCID 4875Potassium Iodide触媒HCID 6228Dimethylformamide溶媒

実験手順

(RS)-1-[2-(5,6-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone, E35 (300 mg, 0.64 mmol) was added slowly to an ice-cooled slurry of sodium hydride (51 mg, 1.3 mmol, 60% dispersion in mineral oil) in DMF (10 ml). After stirring for 0.5 h 1-bromo-2-methoxy-ethane (139 mg, 10 mmol), N,N-diisopropylethylamine (0.3 ml) and potassium iodide (5 mg) was added. The mixture was stirred at room temperature for 0.5 h then 100° C. for 16 h. The volatiles were removed in vacuo from the cooled reaction mixture. The residue was partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate (2×). The combined organics were dried (Na2SO4) and the solvent removed in vacuo. The residue was triturated with ethyl acetate to afford the title compound as a solid (306 mg, 65%).

後処理

  1. additionwas added
  2. wait100° C. for 16 h
  3. customThe volatiles were removed in vacuo from the cooled reaction mixture
  4. customThe residue was partitioned between ethyl acetate and water
  5. extractionThe aqueous phase was extracted with ethyl acetate (2×)
  6. dry with materialThe combined organics were dried (Na2SO4)
  7. customthe solvent removed in vacuo
  8. customThe residue was triturated with ethyl acetate

出典と根拠

ORDレコード
ord-0f42d06da487477e8e311ce8fc4197f1
出典データセット
uspto-grants-2011_04
特許番号
US07928124B2

反応ノート

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