Trimethylsilylacetylene → tert-butyl 3-((trimethylsilyl)ethynyl)-1H-indazole-1-carboxylate

HRID 1520001Notes

Reaction equation

HRID 1520001 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[N:3]=1.[CH3:18][Si:19]([C:22]#[CH:23])([CH3:21])[CH3:20]>C(Cl)Cl.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>[CH3:18][Si:19]([C:22]#[C:23][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[N:3]=1)([CH3:21])[CH3:20]

Participants

5

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 11473390tert-butyl 3-iodo-1H-indazole-1-carboxylate

Product 1

HCID 67981125tert-butyl 3-((trimethylsilyl)ethynyl)-1H-indazole-1-carboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl 3-iodo-1H-indazole-1-carboxylate (prepared as described in J. Med. Chem. (2008), 51(12), 3460-3465); (34 g; 99 mmol; 1.00 eq.), (trimethylsilyl)acetylene (16.6 mL; 119 mmol; 1.20 eq.), PdCl2(PPh3)2 (2.77 g; 3.95 mmol; 0.04 eq.) and TEA (41 mL) was heated overnight at 50° C. The reaction mixture was then diluted with DCM and washed three times with an aqueous saturated solution of NH4Cl. Organic layer was dried over magnesium sulfate, filtered and concentrated. This crude was solubilized in DCM and the precipitate obtained was removed by filtration through a celite pad. Purification by flash chromatography on silica (Heptane/EtOAc; gradient from 98:2 to 2:98) afforded the title compound as a beige solid (20 g, 69% yield). 1H NMR (300 MHz, DMSO-d6) δ: 8.12 (d, J=8.5 Hz, 1H), 7.78 (d, J=8.5 Hz, 1H), 7.70 (m, 1H), 7.46 (m, 1H), 1.65 (s, 9H), 0.32 (s, 9H).

Workup

  1. washwashed three times with an aqueous saturated solution of NH4Cl
  2. dry with materialOrganic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customthe precipitate obtained
  6. customwas removed by filtration through a celite pad
  7. customPurification by flash chromatography on silica (Heptane/EtOAc; gradient from 98:2 to 2:98)

Sources & evidence

ORD record
ord-103a7ddb5c5245d8851f98e9831ea4ad
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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