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 563925ノート

反応式

HRID 563925 の反応式
[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

参加物

6

反応物 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

生成物 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-acetamide収率 11%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-99e4ae8bbf7849f49a359e47a4586298
出典データセット
uspto-grants-2011_11
特許番号
US08067598B2

反応ノート

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