Sodium Carbonate → 6-nitro-3-(pyridin-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole

HRID 1038825Notes

Reaction equation

HRID 1038825 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:11]([O-:13])=[O:12])=[CH:8][CH:9]=2)[N:4]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:3]=1.[N:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N+:11]([C:7]1[CH:6]=[C:5]2[C:10]([C:2]([C:25]3[CH:26]=[CH:27][N:22]=[CH:23][CH:24]=3)=[N:3][N:4]2[CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:9][CH:8]=1)([O-:13])=[O:12]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2734379(Pyridin-4-yl)boronic acidHCID 218774881H-Indazole, 3-iodo-6-nitro-1-[[2-(trimethylsilyl)ethoxy]methyl]-2×

Product 1

HCID 687516696-nitro-3-(pyridin-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazoleYield 84%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a microwave vial was added 3-iodo-6-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (1.2 g, 2.9 mmol, WO 2010/027500, Intermediate 57, Step B), pyridine-4-boronic acid (0.704 g, 5.72 mmol), and Pd(PPh3)4 (0.165 g, 0.143 mmol), 1,4-dioxane (25 mL) and an aqueous solution of Na2CO3 (2 M, 6.3 mL, 12.6 mmol). The vial was sealed and the mixture was heated in a microwave at about 120° C. for about 40 min. The mixture was diluted with EtOAc (100 mL) and water (25 mL) and the layers separated. The aqueous layer was extracted with EtOAc (15 mL). The combined extracts were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by column chromatography (80 g silica gel) eluting with 20 to 80% EtOAc/heptane to provide 6-nitro-3-(pyridin-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (0.893 g, 84%): LC/MS (Table 2, Method c) Rt=3.02 min.; MS m/z: 371 (M+H)+.

Workup

  1. customThe vial was sealed
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with EtOAc (15 mL)
  4. washThe combined extracts were washed with brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by column chromatography (80 g silica gel)
  9. washeluting with 20 to 80% EtOAc/heptane

Sources & evidence

ORD record
ord-7007644f09b2435ca9fad13a79fc73ba
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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