Trimethylsilylacetylene → [3-Methyl-5-(3-trifluoromethyl-phenyl)-6-trimethylsilanylethynyl-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1517069Notes

Reaction equation

HRID 1517069 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[O:9])[C:5]([CH3:21])=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1.[C:32]([Si:34]([CH3:37])([CH3:36])[CH3:35])#[CH:33]>C(N(CC)CC)C.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>[CH3:21][C:5]1[C:6]([C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[O:9])=[N:7][C:2]([C:33]#[C:32][Si:34]([CH3:37])([CH3:36])[CH3:35])=[C:3]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)[CH:4]=1

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 44547211[6-Chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

Product 1

HCID 57441155[3-Methyl-5-(3-trifluoromethyl-phenyl)-6-trimethylsilanylethynyl-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 68%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
125 °C

Procedure

0.90 g (1.99 mmol) of [6-chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 3), 0.042 g (0.06 mmol) of bis(triphenylphosphine)palladium(II) chloride and 0.021 g (0.11 mmol) of copper(I) iodide were suspended in 2.0 ml of triethylamine. After addition of 2.14 ml=1.50 g (15.0 mmol) of ethinyltrimethylsilane, the reaction vessel was sealed, heated up to 125° C. and stirring continued for four days. The reaction mixture was then poured into crashed ice and extracted three times with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1) to give 0.693 g (68%) of the title compound as dark brown oil. MS: 514.4 (MH+).

Workup

  1. customthe reaction vessel was sealed
  2. additionThe reaction mixture was then poured
  3. extractionextracted three times with CH2Cl2
  4. washthe organic phases were washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1)

Sources & evidence

ORD record
ord-be8cf4452c6d4e61a3ef3b88c6e15c30
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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