Triethylamine → {1-[4-(3-Phenyl-7-trimethylsilanylethynyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 872325Notes

Reaction equation

HRID 872325 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24](Br)[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:35][Si:36]([C:39]#[CH:40])([CH3:38])[CH3:37].C(N(CC)CC)C>CN(C=O)C.[Cu]I>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24]([C:40]#[C:39][Si:36]([CH3:38])([CH3:37])[CH3:35])[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 66665545{1-[4-(7-Bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 66665439{1-[4-(3-Phenyl-7-trimethylsilanylethynyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 82.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of {1-[4-(7-bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (100 mg, 0.19 mmol), [1,1-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) CH2Cl2 complex (7.9 mg, 0.01 mmol, 5 mol %) and copper(I) iodide (3.7 mg, 0.019 mmol, 10 mol %) in DMF (2 mL) under an argon atmosphere was added trimethylsilylacetylene (0.08 mL, 0.58 mmol, 3.0 equiv) and triethylamine (0.13 mL, 0.96 mmol, 5.0 equiv). The resulting mixture was heated at 90° C. for 1 h in a microwave apparatus, then concentrated under reduced pressure. The remaining material was separated between water (50 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (50 mL). The combined organic phases were washed with water (25 mL), dried (Na2SO4 anh), and concentrated under reduced pressure. The remaining material (112 mg) was purified using MPLC (Biotage Isolera Flash NH2 Snap 10 reverse phase column; 99% CH2Cl2/1% MeOH for 1 min., gradient to 90% CH2Cl2/10% MeOH over 10 min.; 90% CH2Cl2/10% MeOH for 5.2 min.) to give {1-[4-(3-phenyl-7-trimethylsilanylethynyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (84 mg, 82%):

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe remaining material was separated between water (50 mL) and EtOAc (50 mL)
  3. extractionThe aqueous phase was extracted with EtOAc (50 mL)
  4. washThe combined organic phases were washed with water (25 mL)
  5. dry with materialdried (Na2SO4 anh)
  6. concentrationconcentrated under reduced pressure
  7. customThe remaining material (112 mg) was purified
  8. waitgradient to 90% CH2Cl2/10% MeOH over 10 min.

Sources & evidence

ORD record
ord-e98e80dcefc948969a0754481fa7e29c
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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