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 1517621노트

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HRID 1517621 반응식
[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

참가 물질

7

반응물 4

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

생성물 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-one수율 30.1%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6228Dimethylformamide용매

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온도
130 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-e307071acee34867a0a616ab9e2653f7
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232289B2

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