Triethylamine → 3-methyl-1-((6-methylpyridin-2-yl)methyl)-4-nitro-1H-indazole

HRID 706628

Reaction equation

HRID 706628 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[N:16]=2)[N:3]=1.[C:22]1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C[Sn](C)(C)C.C(N(CC)CC)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[CH3:22][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[N:16]=2)[N:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11661TetramethyltinHCID 80271Tri-o-tolylphosphineHCID 672597623-iodo-1-((6-methylpyridin-2-yl)methyl)-4-nitro-1H-indazole

Product 1

HCID 672592993-methyl-1-((6-methylpyridin-2-yl)methyl)-4-nitro-1H-indazoleYield 394.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A flask equipped with a reflux condenser and a nitrogen line was charged with 3-iodo-1-((6-methylpyridin-2-yl)methyl)-4-nitro-1H-indazole (Example 89, Steps A-B; 100 mg, 0.254 mmol), trio-tolylphosphine (15.4 mg, 0.051 mmol), and tris(dibenzylideneacetone)dipalladium (0) (23 mg, 0.025 mmol). The flask was purged with nitrogen and anhydrous DMF (30 mL), and tetramethylstannane (0.04 ml, 0.28 mmol) were added, followed by triethylamine (0.04 mL, 0.30 mmol). The flask was degassed under nitrogen and heated at 80° C. for 6 hours. The reaction mixture was cooled to ambient temperature, diluted with water, and extracted with DCM and EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate, and concentrated. The crude product was subjected to preparative thin-layer chromatography on silica with 2% MeOH/DCM as eluent to afford 56.8 mg of desired product as a yellow solid.

Workup

  1. customA flask equipped with a reflux condenser
  2. additionwere added
  3. customThe flask was degassed under nitrogen
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. additiondiluted with water
  6. extractionextracted with DCM and EtOAc
  7. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-dc88d900ac2149bf8ad921550e65a844
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Linked notes

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