Hydrochloric Acid → N-(5-bromo-2-(2,2-dimethylmorpholino)pyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine

HRID 1431346Notes

Reaction equation

HRID 1431346 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:16])[C:5]([N:8]2[CH2:13][CH2:12][O:11][C:10]([CH3:15])([CH3:14])[CH2:9]2)=[N:6][CH:7]=1.Cl[C:18]1[C:27]2[C:22](=[CH:23][C:24]([F:29])=[CH:25][C:26]=2[F:28])[N:21]=[C:20]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=2)[C:19]=1[CH3:36].Cl.O1CCOCC1>CN1C(=O)CCC1.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([NH:16][C:18]2[C:27]3[C:22](=[CH:23][C:24]([F:29])=[CH:25][C:26]=3[F:28])[N:21]=[C:20]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[C:19]=2[CH3:36])[C:5]([N:8]2[CH2:13][CH2:12][O:11][C:10]([CH3:14])([CH3:15])[CH2:9]2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 596311955-Bromo-2-(2,2-dimethylmorpholino)pyridin-3-amine

Product 1

HCID 59631452N-(5-bromo-2-(2,2-dimethylmorpholino)pyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

5-Bromo-2-(2,2-dimethylmorpholino)pyridin-3-amine (0.087 g, 0.31 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.071 g, 0.25 mmol), and hydrochloric acid, 4.0M in 1,4-dioxane (0.07 mL, 0.28 mmol) were stirred in NMP (0.5 mL) then microwaved at 150° C. After 2 h, the reaction was diluted with EtOAc and washed once with satd aq. sodium bicarbonate and once with brine. After drying over anhydrous sodium sulfate, filtration, and concentration, the brown residue was purified with silica gel chromatography (0-40% EtOAc in hexanes) to yield mostly N-(5-bromo-2-(2,2-dimethylmorpholino)pyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. Mass Spectrum (ESI) m/e=540.1 (M+1).

Workup

  1. customthen microwaved at 150° C
  2. washwashed once with satd aq. sodium bicarbonate and once with brine
  3. dry with materialAfter drying over anhydrous sodium sulfate, filtration, and concentration
  4. customthe brown residue was purified with silica gel chromatography (0-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9105bceba1fa4d5cbda1f4771073b03c
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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