Cesium carbonate → 4-[[2-[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methyl]morpholin-3-one

HRID 1517621ノート

反応式

HRID 1517621 の反応式
[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:20][CH2:21][C:22]([F:24])([F:23])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:19])=[N:16][NH:17][CH:18]=1)[CH2:9][CH2:8]3.Br[C:26]1[C:31]([CH2:32][N:33]2[CH2:38][CH2:37][O:36][CH2:35][C:34]2=[O:39])=[CH:30][CH:29]=[CH:28][N:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN[C@@H]1CCCC[C@H]1NC>CN(C)C=O.[Cu]I>[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:20][CH2:21][C:22]([F:23])([F:24])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:19])=[N:16][N:17]([C:26]2[C:31]([CH2:32][N:33]4[CH2:38][CH2:37][O:36][CH2:35][C:34]4=[O:39])=[CH:30][CH:29]=[CH:28][N:27]=2)[CH:18]=1)[CH2:9][CH2:8]3

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 582686224-((2-Bromopyridin-3-yl)methyl)morpholin-3-oneHCID 178434546HCID 178434546、化合物

生成物 1

HCID 582686364-[[2-[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methyl]morpholin-3-one収率 30.1%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
130 °C

実験手順

A mixture of 2-chloro-4,4-difluoro-1′-[(3-methyl-1H-pyrazol-4-yl)methyl]spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine] (0.20 g, 0.53 mmol), 4-[(2-bromo-3-pyridyl)methyl]morpholin-3-one (0.21 g, 0.77 mmol), copper(I) iodide (0.015 g, 0.078 mmol) and cesium carbonate (0.36 g, 1.10 mmol) in dimethylformamide (5 mL) is degassed by bubbling argon for 15 minutes. (1R,2R)—N,N′-dimethylcyclohexane-1,2-diamine (0.02 g, 0.14 mmol) is added while degassing for 15 minutes and then the mixture is heated to 130° C. for 16 hours. After completion, the reaction mixture is allowed to cool to room temperature and filtered through celite. The residue is washed with ethyl acetate (2×25 mL) and the filtrate is washed with water (30 mL). The aqueous layer was extracted with ethyl acetate (2×25 mL) and the combined organic extracts are dried over sodium sulfate and concentrated in vacuo. The crude mixture is purified by column chromatography over silica gel eluting with dichloromethane/methanol (96:4) to yield 0.09 g (30%) of the title compound. MS (m/z): 564 (M+1).

後処理

  1. customis degassed
  2. customby bubbling argon for 15 minutes
  3. customwhile degassing for 15 minutes
  4. temperatureto cool to room temperature
  5. filtrationfiltered through celite
  6. washThe residue is washed with ethyl acetate (2×25 mL)
  7. washthe filtrate is washed with water (30 mL)
  8. extractionThe aqueous layer was extracted with ethyl acetate (2×25 mL)
  9. dry with materialthe combined organic extracts are dried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe crude mixture is purified by column chromatography over silica gel eluting with dichloromethane/methanol (96:4)

出典と根拠

ORDレコード
ord-e307071acee34867a0a616ab9e2653f7
出典データセット
uspto-grants-2012_07
特許番号
US08232289B2

反応ノート

読み込み中…