Ethanol → N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(((2-hydroxy ethyl)(methyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 335306Notes

Reaction equation

HRID 335306 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][C:38]=1[F:39])[CH2:5][NH:6][C:7]([C:9]1[CH:10]=[CH:11][C:12]([F:35])=[C:13]([NH:15][C:16]([C:18]2[N:22]3[CH:23]=[CH:24][C:25]([C:27]4[CH:28]=[N:29][C:30](C=O)=[CH:31][CH:32]=4)=[CH:26][C:21]3=[N:20][CH:19]=2)=[O:17])[CH:14]=1)=[O:8].[CH3:40][NH:41][CH2:42][CH2:43][OH:44].[BH4-].[Na+].[CH3:47]CO>>[F:1][C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][C:38]=1[F:39])[CH2:5][NH:6][C:7]([C:9]1[CH:10]=[CH:11][C:12]([F:35])=[C:13]([NH:15][C:16]([C:18]2[N:22]3[CH:23]=[CH:24][C:25]([C:27]4[CH:28]=[N:29][C:30]([CH2:40][N:41]([CH2:42][CH2:43][OH:44])[CH3:47])=[CH:31][CH:32]=4)=[CH:26][C:21]3=[N:20][CH:19]=2)=[O:17])[CH:14]=1)=[O:8]

Participants

5

Reactant 4

HCID 702EthanolHCID 80162-(Methylamino)ethanolHCID 4311764Sodium borohydrideHCID 86695680N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-formylpyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 71283000N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(((2-hydroxy ethyl)(methyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

Conditions

Temperature
70 °C

Procedure

A suspension of N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-formylpyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide (step 1) (100 mg, 0.189 mmol), 2-(methylamino)ethanol (70.9 mg, 0.944 mmol) and molecular sieves in EtOH (2 ml) was heated at 70° C. overnight. The mixture was cooled to 0° C. and treated with sodium borohydride (7.15 mg, 0.189 mmol). The mixture was allowed to warm to RT and was stirred overnight. The resulting suspension was removed by filtration and the filtrate was concentrated in vacuo. The residue was partitioned between EtOAc and water. The organic portion was separated, washed with NaHCO3, dried (MgSO4) and concentrated in vacuo. Purification of the residue by preparative chromatography eluting with 25-50% 0.1% TFA acetonitrile/water afforded fractions that were combined and diluted with NaHCO3 and 5% trifluoroethanol/DCM. The organics were separated, dried and concentrated in vacuo to afford a white solid. The solid was triturated with EtOH/Ether to afford the title compound as a white solid;

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. temperatureto warm to RT
  3. customThe resulting suspension was removed by filtration
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was partitioned between EtOAc and water
  6. customThe organic portion was separated
  7. washwashed with NaHCO3
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification of the residue by preparative chromatography
  11. washeluting with 25-50% 0.1% TFA acetonitrile/water afforded fractions that
  12. additiondiluted with NaHCO3 and 5% trifluoroethanol/DCM
  13. customThe organics were separated
  14. customdried
  15. concentrationconcentrated in vacuo
  16. customto afford a white solid
  17. customThe solid was triturated with EtOH/Ether

Sources & evidence

ORD record
ord-c700d2ea60424333a61977ac799c79a6
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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