Dimethylformamide → 8-[(2,5-difluorobenzyl)oxy]-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

HRID 64481

Reaktionsgleichung

Reaktionsgleichung von HRID 64481
[Si]([O:8][CH2:9][C@H:10]([NH:17][C:18]([C:20]1[N:24]2[CH:25]=[CH:26][CH:27]=[C:28]([OH:29])[C:23]2=[N:22][C:21]=1[CH3:30])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(C(C)(C)C)(C)C.Br[CH2:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=1[F:40].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>[Cl-].[Na+].O.C(Cl)(Cl)Cl.O>[F:40][C:34]1[CH:35]=[CH:36][C:37]([F:39])=[CH:38][C:33]=1[CH2:32][O:29][C:28]1[C:23]2[N:24]([C:20]([C:18]([NH:17][C@H:10]([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:9][OH:8])=[O:19])=[C:21]([CH3:30])[N:22]=2)[CH:25]=[CH:26][CH:27]=1

Komponenten

8

Edukt 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 5228302-(Bromomethyl)-1,4-difluorobenzeneHCID 86713409N-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenylethyl]-8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxamide

Produkt 1

HCID 867135098-[(2,5-difluorobenzyl)oxy]-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamideAusbeute 72,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6212ChloroformLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
30 °C

Versuchsvorschrift

A mixture of 8.5 mg of N-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenylethyl]-8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxamide, 5.6 mg of α-bromo-2,5-difluorotoluene, 5.0 mg of potassium carbonate, and 700 μl of DMF was stirred at 30° C. for 28 hours. To the reaction mixture were added 1 ml of water, 0.5 ml of saturated brine, and 4 ml of chloroform to carry out a layer separation operation. The organic layer was concentrated under reduced pressure, and to the residue were added 300 μl of THF and 300 μl of 1 M hydrochloric acid, followed by stirring at room temperature for 6 hours. To the reaction mixture were added 300 μl of a 1 M aqueous sodium hydroxide solution and 100 of saturated aqueous sodium bicarbonate, followed by extraction with 3 ml of chloroform. The solvent was evaporated under reduced pressure and the obtained residue was purified by preparative HPLC to obtain 6.3 mg of 8-[(2,5-difluorobenzyl)oxy]-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

Aufarbeitung

  1. customa layer separation operation
  2. concentrationThe organic layer was concentrated under reduced pressure
  3. additionto the residue were added 300 μl of THF and 300 μl of 1 M hydrochloric acid
  4. stirringby stirring at room temperature for 6 hours
  5. additionTo the reaction mixture were added 300 μl of a 1 M aqueous sodium hydroxide solution and 100 of saturated aqueous sodium bicarbonate
  6. extractionfollowed by extraction with 3 ml of chloroform
  7. customThe solvent was evaporated under reduced pressure
  8. customthe obtained residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-93954a9d827946b597c2de06d33bb397
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447090B2

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