4-Methylmorpholine → rac-8-[(2,6-Difluorobenzyl)oxy]-N-[2-hydroxy-1-(pyridin-3-yl)ethyl]-2-methylimidazo[1,2-a]-pyridine-3-carboxamide

HRID 1624127Notes

Reaction equation

HRID 1624127 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16](O)=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.F[B-](F)(F)F.N1(O[C+](N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:53][CH:54]([C:57]1[CH:58]=[N:59][CH:60]=[CH:61][CH:62]=1)[CH2:55][OH:56]>CN(C=O)C.O>[F:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:2]([F:1])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:53][CH:54]([C:57]3[CH:58]=[N:59][CH:60]=[CH:61][CH:62]=3)[CH2:55][OH:56])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 27345901-(3-Pyridinyl)-2-hydroxyethylamineHCID 867178728-((2,6-Difluorobenzyl)oxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acidHCID 178484679HCID 178484679, compound

Product 1

HCID 90115765rac-8-[(2,6-Difluorobenzyl)oxy]-N-[2-hydroxy-1-(pyridin-3-yl)ethyl]-2-methylimidazo[1,2-a]-pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

150 mg (0.47 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 227 mg (0.71 mmol) of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU) and 238 mg (2.36 mmol) of 4-methylmorpholine were initially charged in 3 ml of DMF. After 10 min at RT, 98 mg (0.71 mmol) of 2-amino-2-(pyridin-3-yl)ethanol were added and the mixture was stirred at room temperature overnight. About 25 ml of water were added to the reaction solution and the precipitate formed was stirred for another 30 min, filtered off, washed thoroughly with water and dried under high vacuum overnight. The crude product was purified by silica gel chromatography (mobile phase: dichloromethane:methanol gradient). The product fractions were concentrated and stirred with acetonitrile. The solid obtained was filtered off and dried. This gave 40 mg of the target compound (20% of theory, purity 100%).

Workup

  1. customthe precipitate formed
  2. stirringwas stirred for another 30 min
  3. filtrationfiltered off
  4. washwashed thoroughly with water
  5. customdried under high vacuum overnight
  6. customThe crude product was purified by silica gel chromatography (mobile phase: dichloromethane:methanol gradient)
  7. concentrationThe product fractions were concentrated
  8. stirringstirred with acetonitrile
  9. customThe solid obtained
  10. filtrationwas filtered off
  11. customdried

Sources & evidence

ORD record
ord-e5cddc84e7974436b503583943fb76a6
Source dataset
uspto-grants-2014_07
Patent number
US08778964B2

Reaction notes

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