Ammonium Chloride → 6-{[3-chloro-5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-pyrazin-2-ylquinazoline-4-amine

HRID 81656

Reaction equation

HRID 81656 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([O:9][CH2:10][CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])=[CH:4][N:3]=1.CC(C)([O-])C.[K+].[N:24]1[CH:29]=[CH:28][N:27]=[CH:26][C:25]=1[NH:30][C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([OH:41])[CH:39]=2)[N:34]=[CH:33][N:32]=1.[Cl-].[NH4+]>CN(C)C(=O)C>[Cl:8][C:7]1[C:2]([O:41][C:38]2[CH:39]=[C:40]3[C:35](=[CH:36][CH:37]=2)[N:34]=[CH:33][N:32]=[C:31]3[NH:30][C:25]2[CH:26]=[N:27][CH:28]=[CH:29][N:24]=2)=[N:3][CH:4]=[C:5]([O:9][CH2:10][CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])[CH:6]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 23665647Potassium tert-butoxideHCID 866458962,3-Dichloro-5-(2,2-diethoxyethoxy)pyridineHCID 1363347444-(Pyrazin-2-ylamino)quinazolin-6-ol

Product 1

HCID 684306576-{[3-chloro-5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-pyrazin-2-ylquinazoline-4-amineYield 10%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
200 °C

Procedure

2,3-Dichloro-5-(2,2-diethoxyethoxy)pyridine (810 mg, 2.9 mmol) and potassium tert-butoxide (350 mg, 3.1 mmol) were added to an N,N-dimethylacetamide suspension (3 ml) of 4-(pyrazin-2-ylamino)quinazolin-6-ol (300 mg, 1.25 mmol), and stirred for 24 hours in a sealed tube at 200° C. The reaction solution was cooled to room temperature, aqueous saturated ammonium chloride solution was added, filtered, and washed with a mixed solution of chloroform/methanol (9:1). The obtained filtrate was extracted with chloroform, 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 reversed-phase liquid chromatography (YMC CombiPrep Pro C18 AS-360-cc) to obtain 6-{[3-chloro-5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-pyrazin-2-ylquinazoline-4-amine (60 mg, yield: 10%) as a pale yellow solid.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. filtrationfiltered
  3. washwashed with a mixed solution of chloroform/methanol (9:1)
  4. extractionThe obtained filtrate was extracted with chloroform
  5. washthe organic layer was washed with water and saturated saline water
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by reversed-phase liquid chromatography (YMC CombiPrep Pro C18 AS-360-cc)

Sources & evidence

ORD record
ord-c6a64b49652946daa6df266cc8c90601
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Linked notes

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