Sodium Hydroxide → 2-[(E)-1-[3-[1-(5,7-difluoroquinolin-6-yl)ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino]oxyethanol

HRID 1959738Notes

Reaction equation

HRID 1959738 reaction equation
[F:1][C:2]1[C:11]([CH:12]([C:14]2[N:18]3[N:19]=[C:20]([C:23](=O)[CH3:24])[CH:21]=[CH:22][C:17]3=[N:16][N:15]=2)[CH3:13])=[C:10]([F:26])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.Cl.[NH2:28][O:29][CH2:30][CH2:31][OH:32].[OH-].[Na+]>CO>[OH:32][CH2:31][CH2:30][O:29]/[N:28]=[C:23](/[C:20]1[CH:21]=[CH:22][C:17]2[N:18]([C:14]([CH:12]([C:11]3[C:2]([F:1])=[C:3]4[C:8](=[CH:9][C:10]=3[F:26])[N:7]=[CH:6][CH:5]=[CH:4]4)[CH3:13])=[N:15][N:16]=2)[N:19]=1)\[CH3:24]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 22507086Ethanol, 2-(aminooxy)-, hydrochloride2×HCID 581904661-(3-(1-(5,7-Difluoroquinolin-6-yl)ethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

Product 1

HCID 581905272-[(E)-1-[3-[1-(5,7-difluoroquinolin-6-yl)ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino]oxyethanolYield 98%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 1-{3-[1-(5,7-difluoro-quinolin-6-yl)-ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl}-ethanone (4.2 g, 11.9 mmol) in methanol (250 mL) was added 2-(aminooxy)ethanol hydrochloride (intermediate S) (2.70 g, 23.8 mmol). The mixture was stirred at rt overnight. LC-MS showed the reaction was complete. An aqueous 1N NaOH solution was added slowly until pH 8-9. The mixture was concentrated, extracted with EtOAc, washed with water and brine. The organic layer was dried over anhydrous Na2SO4, filtered, concentrated, and purified by gradient column chromatography (EtOAc:hexane=2:1, then 100% EtOAc, and then MeOH:EtOAc=1:12 as eluent) to afford 4.8 g (98%) of the title compound as a white solid. 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.97 (dd, 1H), 8.44 (m, 1H), 8.25 (d, 1H), 7.64-7.70 (m, 2H), 7.59 (dd, 1H), 5.25 (q, 1H), 4.70 (t, 1H), 4.19 (t, 2H), 3.62 (dd, 2H), 2.02 (d, 3H), 1.88 (s, 3H). LCMS (method A): [MH]+=413, tR=5.09 min.

Workup

  1. concentrationThe mixture was concentrated
  2. extractionextracted with EtOAc
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by gradient column chromatography (EtOAc

Sources & evidence

ORD record
ord-1e8ea7f3819a430091ea6b8a1f006489
Source dataset
uspto-grants-2013_04
Patent number
US08410264B2

Reaction notes

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