Sodium Iodide → N-methyl-2-{2-methyl-4-[2-(4-trifluoromethyl-phenyl)-ethyl]-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl}-2-phenyl-acetamide

HRID 563925Notes

Reaction equation

HRID 563925 reaction equation
[CH3:1][C:2]1[S:10][C:9]2[CH2:8][CH2:7][NH:6][CH:5]([CH2:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)[C:4]=2[CH:3]=1.Br[CH:24]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:25]([NH:27][CH3:28])=[O:26].C(N(C(C)C)C(C)C)C.[I-].[Na+]>C(#N)C>[CH3:28][NH:27][C:25](=[O:26])[CH:24]([N:6]1[CH2:7][CH2:8][C:9]2[S:10][C:2]([CH3:1])=[CH:3][C:4]=2[CH:5]1[CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 124711602-Bromo-N-methyl-2-phenylacetamideHCID 598199942-Methyl-4-[2-(4-trifluoromethyl-phenyl)-ethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine

Product 1

HCID 25027322N-methyl-2-{2-methyl-4-[2-(4-trifluoromethyl-phenyl)-ethyl]-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl}-2-phenyl-acetamideYield 11%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 300 mg (0.92 mmol) 2-methyl-4-[2-(4-trifluoromethyl-phenyl)-ethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine in 13 mL acetonitrile was added 210.3 mg (0.92 mmol) 2-Bromo-N-methyl-2-phenyl-acetamide (commercially available), 473 uL (2.76 mmol) N-ethyldiisopropylamine and 138 mg (0.92 mmol) sodium iodide. The solution was stirred for 18 h at 60° C. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate and washed with water and Na2CO3 aq. The organic layer was dried over Na2SO4, filtered and evaporated. The residue was purified on silica eluting with a gradient formed from heptane and ethyl acetate. The diastereoisomeric product eluting first (obtained after evaporation from the product containing fractions) was dissolved in methanol, treated with Norit, heated to reflux, filtered and evaporated to dryness to yield 46 mg (11%) of N-methyl-2-{2-methyl-4-[2-(4-trifluoromethyl-phenyl)-ethyl]-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl}-2-phenyl-acetamide (diastereoisomer 1) (MS(m/e): 472.9 (MH+)) as light yellow oil.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed with water and Na2CO3 aq. The organic layer
  4. dry with materialwas dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified on silica eluting with a gradient
  8. customformed from heptane and ethyl acetate
  9. washThe diastereoisomeric product eluting first (
  10. customobtained
  11. customafter evaporation from the product
  12. additioncontaining fractions)
  13. dissolutionwas dissolved in methanol
  14. additiontreated with Norit
  15. temperatureheated
  16. temperatureto reflux
  17. filtrationfiltered
  18. customevaporated to dryness

Sources & evidence

ORD record
ord-99e4ae8bbf7849f49a359e47a4586298
Source dataset
uspto-grants-2011_11
Patent number
US08067598B2

Reaction notes

Loading…