Trimethylsilylacetylene → tert-butyl 5-[1-(tert-butoxycarbonyl)piperidin-4-yl]-3-[(trimethylsilyl)ethynyl]-1H-indazole-1-carboxylate

HRID 1520019Notes

Reaction equation

HRID 1520019 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[N:18]=[C:17]3I)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:31][Si:32]([C:35]#[CH:36])([CH3:34])[CH3:33]>CCOC(C)=O.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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[N:18]=[C:17]3[C:36]#[C:35][Si:32]([CH3:34])([CH3:33])[CH3:31])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 67981049Tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-iodo-1h-indazole-1-carboxylate

Product 1

HCID 67981297tert-butyl 5-[1-(tert-butoxycarbonyl)piperidin-4-yl]-3-[(trimethylsilyl)ethynyl]-1H-indazole-1-carboxylateYield 105.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of tert-butyl 5-[1-(tert-butoxycarbonyl)piperidin-4-yl]-3-iodo-1H-indazole-1-carboxylate (200 mg; 0.38 mmol; 1.0 eq.), (Trimethylsilyl)acetylene (53 μl; 0.38 mmol; 1.0 eq.), TEA (158 μl) and bis(triphenylphosphine)palladium(II) chloride (10.7 mg; 0.02 mmol; 0.04 eq.) was heated at 70° C. overnight in a sealed tube. The reaction mixture was diluted with EtOAc and washed with a saturated solution of NH4Cl and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated to give the tittle compound as a brown gum (200 mg, 100%). 1H NMR (300 MHz, DMSO-d6) δ 8.04 (d, J=8.7 Hz, 1H), 7.63-7.54 (m, 2H), 4.15-4.04 (m, 2H), 2.99-2.74 (m, 3H), 1.86-1.74 (m, 2H), 1.64 (s, 9H), 1.61-1.52 (m, 2H), 1.42 (s, 9H), 0.32 (s, 9H).

Workup

  1. washwashed with a saturated solution of NH4Cl and brine
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-e023947a16c24734b0d3f8d1c93662ce
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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