Triethylamine → Tert-butyl 3-(2-(dimethylamino)acetamido)-5-((trimethylsilyl)ethynyl)-1h-indazole-1-carboxylate

HRID 240783Notes

Reaction equation

HRID 240783 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[N:6]=[C:5]2[NH:18][C:19](=[O:24])[CH2:20][N:21]([CH3:23])[CH3:22].C(N(CC)CC)C.[C:32]([Si:34]([CH3:37])([CH3:36])[CH3:35])#[CH:33]>ClCCl.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.[Cu]I>[CH3:22][N:21]([CH3:23])[CH2:20][C:19]([NH:18][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:33]#[C:32][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:3]=2)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[N:6]=1)=[O:24]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 68735653Tert-butyl 5-bromo-3-(2-(dimethylamino)acetamido)-1h-indazole-1-carboxylate

Product 1

HCID 68736669Tert-butyl 3-(2-(dimethylamino)acetamido)-5-((trimethylsilyl)ethynyl)-1h-indazole-1-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of Example 282C (2.56 g, 6.44 mmol), bis(triphenylphosphine)palladium(II) chloride (0.225 g, 0.321 mmol), and copper(I) iodide (0.073 g, 0.383 mmol) was added triethylamine (20 mL, 144 mmol) followed by ethynyltrimethylsilane (0.760 g, 7.73 mmol). The reaction mixture was heated at about 60° C. for about 3 hours. The reaction mixture was diluted with dichloromethane (100 mL), washed with water (20 mL) and brine (20 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with ethyl acetate in dichloromethane (10%) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.69 (s, 1H), 8.08 (s, 1H), 8.04 (d, 1H, J=9.0), 7.62 (d, 1H, J=8.8), 3.21 (s, 2H), 2.30 (s, 6H), 1.61 (s, 9H), 0.23 (s, 9H).

Workup

  1. washwashed with water (20 mL) and brine (20 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with ethyl acetate in dichloromethane (10%)

Sources & evidence

ORD record
ord-ed857ab95de14a45823feea478c94715
Source dataset
uspto-grants-2014_02
Patent number
US08648069B2

Reaction notes

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