Ammonium Chloride → 6-({3-chloro-5-[2-(1,3-dioxolan-2-yl)ethoxy]pyridin-2-yl}oxy)-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine

HRID 81633Notes

Reaction equation

HRID 81633 reaction equation
[Cl:1][C:2]1[C:3](F)=[N:4][CH:5]=[C:6]([O:8][CH2:9][CH2:10][CH:11]2[O:15][CH2:14][CH2:13][O:12]2)[CH:7]=1.CC(C)([O-])C.[K+].[CH3:23][N:24]1[CH:28]=[CH:27][C:26]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][CH:36]=[C:37]([OH:40])[CH:38]=3)[N:33]=[CH:32][N:31]=2)=[N:25]1.[Cl-].[NH4+]>CN(C)C(=O)C>[Cl:1][C:2]1[C:3]([O:40][C:37]2[CH:38]=[C:39]3[C:34](=[CH:35][CH:36]=2)[N:33]=[CH:32][N:31]=[C:30]3[NH:29][C:26]2[CH:27]=[CH:28][N:24]([CH3:23])[N:25]=2)=[N:4][CH:5]=[C:6]([O:8][CH2:9][CH2:10][CH:11]2[O:15][CH2:14][CH2:13][O:12]2)[CH:7]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 231603824-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-olHCID 23665647Potassium tert-butoxideHCID 684276893-Chloro-5-[2-(1,3-dioxolan-2-yl)ethoxy]-2-fluoropyridine

Product 1

HCID 687407606-({3-chloro-5-[2-(1,3-dioxolan-2-yl)ethoxy]pyridin-2-yl}oxy)-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amineYield 73%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

3-Chloro-5-[2-(1,3-dioxolan-2-yl)ethoxy]-2-fluoropyridine (4.6 g, 18.4 mmol) and potassium tert-butoxide (2.6 g, 23 mmol) were added to an N,N-dimethylacetamide suspension (5 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (2.2 g, 9.1 mmol), and reacted at 200° C. for 2 hours, using microwaves. The reaction solution was cooled to room temperature, aqueous saturated ammonium chloride solution was added, and extracted with ethyl acetate. The organic layer was washed with water and saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=75:25) to obtain 6-({3-chloro-5-[2-(1,3-dioxolan-2-yl)ethoxy]pyridin-2-yl}oxy)-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine (3.1 g, yield: 73%) as a yellow solid.

Workup

  1. customreacted at 200° C. for 2 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water and saturated saline water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=75:25)

Sources & evidence

ORD record
ord-71ce770046fe4e3e948f1f601f5bf89c
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Reaction notes

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