Dimethylformamide → 8-(Cyclobutylmethoxy)-N-[(2R)-1-hydroxyhexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

HRID 1624133ノート

反応式

HRID 1624133 の反応式
[OH:1][C:2]1[C:3]2[N:4]([C:8]([C:12]([NH:14][C@H:15]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:29][CH:30]1[CH2:33][CH2:32][CH2:31]1.CN(C=O)C>O>[CH:30]1([CH2:29][O:1][C:2]2[C:3]3[N:4]([C:8]([C:12]([NH:14][C@H:15]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:33][CH2:32][CH2:31]1

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 2734658(Bromomethyl)cyclobutaneHCID 867181768-hydroxy-N-[(2R)-1-hydroxyhexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

生成物 1

HCID 742227148-(Cyclobutylmethoxy)-N-[(2R)-1-hydroxyhexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

100 mg (0.34 mmol) of 8-hydroxy-N-[(2R)-1-hydroxyhexan-2-yl]-2-methylimidazo[1,2-a]-pyridine-3-carboxamide, 246 mg (0.76 mmol) of caesium carbonate and 56 mg (0.38 mmol) of (bromomethyl)cyclobutane were added to 4.9 ml of dry DMF and the mixture was stirred for 60 min in an oil bath preheated to 60° C. After cooling, about 40 ml of water were added to the reaction mixture and the solution formed was extracted 3× with ethyl acetate. The combined organic phases were concentrated and the residue was purified by preparative HPLC (RP18 column, mobile phase: water/methanol gradient with addition of 0.1% TFA). All product-containing fractions were combined and concentrated. Saturated aqueous sodium bicarbonate solution was added to the residue, and the mixture was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate, filtered, concentrated and dried under high vacuum. This gave 78 mg of the target compound (63% of theory, purity 100%).

後処理

  1. custompreheated to 60° C
  2. temperatureAfter cooling
  3. customthe solution formed
  4. extractionwas extracted 3× with ethyl acetate
  5. concentrationThe combined organic phases were concentrated
  6. customthe residue was purified by preparative HPLC (RP18 column, mobile phase: water/methanol gradient with addition of 0.1% TFA)
  7. concentrationconcentrated
  8. additionSaturated aqueous sodium bicarbonate solution was added to the residue
  9. extractionthe mixture was extracted three times with ethyl acetate
  10. dry with materialThe combined organic phases were dried over sodium sulphate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customdried under high vacuum

出典と根拠

ORDレコード
ord-79213d93fe5947d2a098e90ecdfef9d9
出典データセット
uspto-grants-2014_07
特許番号
US08778964B2

反応ノート

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