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

HRID 2079748Notes

Reaction equation

HRID 2079748 reaction equation
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]

Participants

8

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-6a52857fbb7d40d69a62b36f8c904910
Source dataset
uspto-grants-2011_04
Patent number
US07932274B2

Reaction notes

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