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Potassium Phosphate, Tribasic → 6-[2-Ethyl-5-fluoro-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carbonitrile

HRID 340060
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HRID 340060 반응식
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:17]#[N:18])=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][CH:3]=1.[CH2:19]([C:21]1[CH:26]=[C:25]([O:27][CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:24]([F:36])=[CH:23][C:22]=1B1OC(C)(C)C(C)(C)O1)[CH3:20].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:19]([C:21]1[CH:26]=[C:25]([O:27][CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:33])([CH3:35])[CH3:34])[C:24]([F:36])=[CH:23][C:22]=1[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:17]#[N:18])=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][CH:3]=1)[CH3:20]
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참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 712377736-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbonitrileHCID 86676270(2-((5-Ethyl-2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methoxy)ethyl)trimethylsilane

생성물 1

HCID 866762696-[2-Ethyl-5-fluoro-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carbonitrile수율 81.1%

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

To a solution of 6-bromo-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carbonitrile (Preparation 2, 28.5 g, 93 mmol) and 2-[2-ethyl-5-fluoro-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Preparation 5, 73.8 g, 112 mmol) in dioxane (500 mL) was added a solution of potassium phosphate (59.2 g, 279 mmol) in water (120 mL). The mixture was degassed with nitrogen and then tetrakis (triphenylphosphine) palladium(0) (10.8 g, 9.3 mmol) was added. The reaction mixture was heated at 110° C. for 18 hours. The reaction mixture was concentrated in vacuo and the residue was redissolved in EtOAc (1 L) and filtered through Arbocel®, washing with EtOAc (2×500 mL). The combined organic phases were concentrated in vacuo to give a brown oil. The residue was purified by column chromatography on silica gel eluting with 10% EtOAc in heptane to give the title compound as a viscous oil (37.4 g) in an 81% yield.

후처리

  1. customThe mixture was degassed with nitrogen
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue was redissolved in EtOAc (1 L)
  4. filtrationfiltered through Arbocel®
  5. washwashing with EtOAc (2×500 mL)
  6. concentrationThe combined organic phases were concentrated in vacuo
  7. customto give a brown oil
  8. customThe residue was purified by column chromatography on silica gel eluting with 10% EtOAc in heptane

출처 및 근거

ORD 기록
ord-4433fbaaafb1420f8a7aa9095d24d43b
출처 데이터셋
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08895544B2

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