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Cesium carbonate → 5-((R)-1-(3,5-Dichloropyridin-4-yl)ethoxy)-1-(tetrahydro-2H-pyran-2-yl)-3-((E)-2-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)vinyl)-1H-indazole

HRID 41515
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HRID 41515 반응식
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([OH:16])=[CH:13][CH:14]=2)[C:9](/[CH:17]=[CH:18]/[C:19]2[CH:20]=[N:21][N:22]([CH2:24][CH2:25][O:26][CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][O:28]3)[CH:23]=2)=[N:8]1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[C@H:44]([C:46]1[C:51]([Cl:52])=[CH:50][N:49]=[CH:48][C:47]=1[Cl:53])[CH3:45])(=O)=O>C(#N)C>[Cl:53][C:47]1[CH:48]=[N:49][CH:50]=[C:51]([Cl:52])[C:46]=1[C@H:44]([O:16][C:12]1[CH:11]=[C:10]2[C:15](=[CH:14][CH:13]=1)[N:7]([CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][O:1]1)[N:8]=[C:9]2/[CH:17]=[CH:18]/[C:19]1[CH:20]=[N:21][N:22]([CH2:24][CH2:25][O:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][O:28]2)[CH:23]=1)[CH3:45]
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참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 66831604(E)-1-(Tetrahydro-2H-pyran-2-yl)-3-(2-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)vinyl)-1H-indazol-5-olHCID 86647459(S)-1-(3,5-Dichloropyridin-4-yl)ethyl methanesulfonate

생성물 1

HCID 666468355-((R)-1-(3,5-Dichloropyridin-4-yl)ethoxy)-1-(tetrahydro-2H-pyran-2-yl)-3-((E)-2-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)vinyl)-1H-indazole

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

In a 3-neck 250 mL round bottom flask equipped with an internal temperature probe, reflux condenser, nitrogen blanket and magnetic stir bar, slurry (E)-1-(tetrahydro-2H-pyran-2-yl)-3-(2-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)vinyl)-1H-indazol-5-ol (10.0 g, 22.83 mmol) and cesium carbonate (7.88 g, 23.94 mmol) in ACN (92 mL) and warm to 60° C. To the suspension, add (S)-1-(3,5-dichloropyridin-4-yl)ethyl methanesulfonate (7.03 g, 26.02 mmol) and stir overnight. Cool the reaction mixture to RT, filter and wash solids with ACN. Concentrate the filtrate and purify the residue by silica gel chromatography (2-4% (2 M ammonia in methanol)/DCM). Combine product fractions and concentrate in vacuo to a white foam. Yield: 12.5 g (86%). MS (ES) m/z 612 [M+1]+.

후처리

  1. customIn a 3-neck 250 mL round bottom flask equipped with an internal temperature probe
  2. temperaturereflux condenser
  3. filtrationfilter
  4. washwash solids with ACN
  5. concentrationConcentrate the filtrate
  6. custompurify the residue by silica gel chromatography (2-4% (2 M ammonia in methanol)/DCM)
  7. concentrationCombine product fractions and concentrate in vacuo to a white foam

출처 및 근거

ORD 기록
ord-b82d4bc42ae14b6a84ab704cf5f6d9cf
출처 데이터셋
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08530665B2

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