Ammonium Chloride → 6-{[5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)quinazoline-4-amine

HRID 81660Notes

Reaction equation

HRID 81660 reaction equation
[CH2:1]([O:3][CH:4]([O:14][CH2:15][CH3:16])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10](F)=[N:11][CH:12]=1)[CH3:2].CC(C)([O-])C.[K+].[CH3:23][C:24]1[N:28]=[C:27]([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)[S:26][N:25]=1.[Cl-].[NH4+]>CN(C)C(=O)C>[CH2:1]([O:3][CH:4]([O:14][CH2:15][CH3:16])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([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:27]2[S:26][N:25]=[C:24]([CH3:23])[N:28]=2)=[N:11][CH:12]=1)[CH3:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 23665647Potassium tert-butoxideHCID 684297065-(2,2-Diethoxyethoxy)-2-fluoropyridineHCID 68431305HCID 68431305, compound

Product 1

HCID 684306076-{[5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)quinazoline-4-amineYield 40%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

5-(2,2-diethoxyethoxy)-2-fluoropyridine (530 mg, 2.3 mmol) and potassium tert-butoxide (260 mg, 2.3 mmol) were added to an N,N-dimethylacetamide suspension (0.5 ml) of 4-[(3-methyl-1,2,4-thiadiazol-5-yl)amino]quinazolin-6-ol (300 mg, 1.2 mmol), and reacted at 200° C. for 30 minutes, using microwaves. 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 silica gel column chromatography (chloroform:methanol=90:10) to obtain 6-{[5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-(3-methyl-1,2,4-thiadiazol-5-yl)quinazoline-4-amine (220 mg, yield: 40%) as a pale yellow solid.

Workup

  1. customreacted at 200° C. for 30 minutes
  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 silica gel column chromatography (chloroform:methanol=90:10)

Sources & evidence

ORD record
ord-9a3463cabfd74274a58664fc68f55b18
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Reaction notes

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