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

HRID 1517115Notes

Reaction equation

HRID 1517115 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([Sn](CCCC)(CCCC)[C:37]1[CH:42]=[N:41][CH:40]=[CH:39][N:38]=1)CCC>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[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:37]2[CH:42]=[N:41][CH:40]=[CH:39][N:38]=2)=[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

5

Reactant 2

HCID 27373162-(Tributylstannyl)pyrazineHCID 44547211[6-Chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

Product 1

HCID 44547647[3-Methyl-6-pyrazin-2-yl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 50.5%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of 0.20 g (0.44 mmol) of [6-chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 3) in 8.0 ml of DMF was added 0.051 g (0.044 mmol) of tetrakis-(triphenylphosphine)-palladium and the reaction mixture was stirred for 20 min at RT. Then, 0.49 g (1.32 mmol) of 2-tributylstannanyl-pyrazine were added and the reaction was heated up to 100° C. After 6 hours, it was cooled down to RT, poured into crashed ice and extracted three times with EtOAc; 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 0.11 g (50%) of the title compound as yellow oil. MS: 496.2 (MH−).

Workup

  1. temperaturethe reaction was heated up to 100° C
  2. waitAfter 6 hours
  3. temperatureit was cooled down to RT
  4. additionpoured
  5. extractionextracted three times with EtOAc
  6. washthe organic phases were washed with water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1)

Sources & evidence

ORD record
ord-f92cfb1354e34de6ace0f3171e2e4ade
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

Loading…