Dimethylformamide → N-[(2R)-1-Hydroxyhexan-2-yl]-2-methyl-8-(3-methylbutoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 1624134Notes

Reaction equation

HRID 1624134 reaction equation
[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+].I[CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32].CN(C=O)C>O>[OH:17][CH2:16][C@H:15]([NH:14][C:12]([C:8]1[N:4]2[CH:5]=[CH:6][CH:7]=[C:2]([O:1][CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])[C:3]2=[N:10][C:9]=1[CH3:11])=[O:13])[CH2:18][CH2:19][CH2:20][CH3:21]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 109241-Iodo-3-methylbutaneHCID 867181768-hydroxy-N-[(2R)-1-hydroxyhexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 86718225N-[(2R)-1-Hydroxyhexan-2-yl]-2-methyl-8-(3-methylbutoxy)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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 75 mg (0.38 mmol) of 1-iodo-3-methylbutane were added to 4.9 ml of dry DMF, and the mixture was stirred for 30 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 three times 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 82 mg of the target compound (66% of theory, purity 100%).

Workup

  1. custompreheated to 60° C
  2. temperatureAfter cooling
  3. customthe solution formed
  4. extractionwas extracted three times 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

Sources & evidence

ORD record
ord-59a56d1bd0f5486ca6d92661ca539fb1
Source dataset
uspto-grants-2014_07
Patent number
US08778964B2

Reaction notes

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