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

HRID 81658Notes

Reaction equation

HRID 81658 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+].[CH3:24][O:25][C:26]1[N:31]=[C:30]2[S:32][C:33]([NH:35][C:36]3[C:45]4[C:40](=[CH:41][CH:42]=[C:43]([OH:46])[CH:44]=4)[N:39]=[CH:38][N:37]=3)=[N:34][C:29]2=[CH:28][CH:27]=1.[Cl-].[NH4+]>CN(C)C(=O)C>[Cl:8][C:7]1[C:2]([O:46][C:43]2[CH:44]=[C:45]3[C:40](=[CH:41][CH:42]=2)[N:39]=[CH:38][N:37]=[C:36]3[NH:35][C:33]2[S:32][C:30]3[C:29]([N:34]=2)=[CH:28][CH:27]=[C:26]([O:25][CH3:24])[N:31]=3)=[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 866458994-[(5-Methoxy[1,3]thiazolo[5,4-b]pyridin-2-yl)amino]quinazolin-6-ol

Product 1

HCID 866458986-{[3-chloro-5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-(5-methoxy[1,3]thiazolo[5,4-b]pyridin-2-yl)quinazoline-4-amineYield 2.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
200 °C

Procedure

2,3-Dichloro-5-(2,2-diethoxyethoxy)pyridine (240 mg, 0.85 mmol) and potassium tert-butoxide (100 mg, 0.92 mmol) were added to an N,N-dimethylacetamide suspension (1 ml) of 4-[(5-methoxy[1,3]thiazolo[5,4-b]pyridin-2-yl)amino]quinazolin-6-ol (120 mg, 0.37 mmol), and stirred for 24 hours at 200° C. in a sealed tube. The reaction solution was cooled to room temperature, then 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-(5-methoxy[1,3]thiazolo[5,4-b]pyridin-2-yl)quinazoline-4-amine (5 mg, yield: 2%) 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-de05fcc3018e4eaf99348697c0acca0a
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Reaction notes

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