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Sodium Carbonate → cyclopropanecarboxylic acid [4-bromo-3-(2-methyl-2H-indazol-5-yl)-isothiazol-5-yl]-amide

HRID 2079748
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HRID 2079748 반응식
Br[C:2]1[C:6]([Br:7])=[C:5]([NH:8][C:9]([CH:11]2[CH2:13][CH2:12]2)=[O:10])[S:4][N:3]=1.[CH3:14][N:15]1[CH:23]=[C:22]2[C:17]([CH:18]=[CH:19][C:20](B3OC(C)(C)C(C)(C)O3)=[CH:21]2)=[N:16]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.[Cl-].[Na+].O.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:7][C:6]1[C:2]([C:20]2[CH:19]=[CH:18][C:17]3[C:22](=[CH:23][N:15]([CH3:14])[N:16]=3)[CH:21]=2)=[N:3][S:4][C:5]=1[NH:8][C:9]([CH:11]1[CH2:13][CH2:12]1)=[O:10]
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참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 441182532-Methyl-2H-indazole-5-boronic acid, pinacol esterHCID 66838483Cyclopropanecarboxylic acid (3,4-dibromo-isothiazol-5-yl)-amide

생성물 1

HCID 66838434cyclopropanecarboxylic acid [4-bromo-3-(2-methyl-2H-indazol-5-yl)-isothiazol-5-yl]-amide수율 50%

시약·촉매·용매 4

HCID 178418476
HCID 178418476, 화합물
촉매
HCID 8857Ethyl Acetate용매
HCID 312751,4-Dioxane용매
HCID 57417360Sodium chloride; water용매

실험 절차

Degas by bubbling nitrogen for 10; min through a mixture of cyclopropanecarboxylic acid (3,4-dibromo-isothiazol-5-yl)-amide (1.04; g, 3.19; mmol) and 2-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (1.29; g, 3.51 mmol) in 1,4-dioxane (16; mL) and a 2M aqueous solution of sodium carbonate (7.98 mL). Add bis(triphenylphosphine)palladium(II) chloride (448; mg, 0.64; mmol) and heat at 80° C. for 12; h. Cool, dilute with brine and ethyl acetate and separate the layers. Extract the aqueous phase twice with ethyl acetate. Dry the combined organic phases over sodium sulfate, filter, concentrate and purify by silica gel chromatography, gradient eluting from 40:60; to 100:0; using ethyl acetate:hexanes, to give the title compound as a solid (0.6; g, 1.59; mmol, 50%). MS (m/z): 377, 379; (M+1).

후처리

  1. customDegas
  2. customby bubbling nitrogen for 10
  3. temperatureCool
  4. customseparate the layers
  5. extractionExtract the aqueous phase twice with ethyl acetate
  6. dry with materialDry the combined organic phases over sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate
  9. custompurify by silica gel chromatography
  10. washgradient eluting from 40:60

출처 및 근거

ORD 기록
ord-6a52857fbb7d40d69a62b36f8c904910
출처 데이터셋
uspto-grants-2011_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07932274B2

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