4-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol → 6-{[3-chloro-5-(2-methoxyethoxy)pyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine

HRID 81663Notes

Reaction equation

HRID 81663 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([O:9][CH2:10][CH2:11][O:12][CH3:13])=[CH:4][N:3]=1.CC(C)([O-])C.[K+].[CH3:20][N:21]1[CH:25]=[CH:24][C:23]([NH:26][C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[C:34]([OH:37])[CH:35]=3)[N:30]=[CH:29][N:28]=2)=[N:22]1.O.[Cl-].[Na+]>C(Cl)(Cl)Cl.CN(C)C(=O)C>[Cl:8][C:7]1[C:2]([O:37][C:34]2[CH:35]=[C:36]3[C:31](=[CH:32][CH:33]=2)[N:30]=[CH:29][N:28]=[C:27]3[NH:26][C:23]2[CH:24]=[CH:25][N:21]([CH3:20])[N:22]=2)=[N:3][CH:4]=[C:5]([O:9][CH2:10][CH2:11][O:12][CH3:13])[CH:6]=1

Participants

7

Reactant 4

HCID 231603824-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-olHCID 23665647Potassium tert-butoxideHCID 57417360Sodium chloride; waterHCID 866459022,3-Dichloro-5-(2-methoxyethoxy)pyridine

Product 1

HCID 595088886-{[3-chloro-5-(2-methoxyethoxy)pyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amineYield 28.1%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
180 °C

Procedure

2,3-Dichloro-5-(2-methoxyethoxy)pyridine (127 mg, 0.57 mmol) and potassium tert-butoxide (70 mg, 0.62 mmol) were added to an N,N-dimethylacetamide solution (2 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (60 mg, 0.25 mmol), and stirred overnight at 180° C. under a nitrogen atmosphere in a sealed tube. The reaction solution was cooled with ice, then sodium chloride water and chloroform were added, the organic layer was washed with 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 the entitled compound (30 mg, yield: 28%) as a pale orange amorphous solid.

Workup

  1. temperatureThe reaction solution was cooled with ice
  2. washthe organic layer was washed with water
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by reversed-phase liquid chromatography (YMC CombiPrep Pro C18 AS-360-CC)

Sources & evidence

ORD record
ord-8cfc7015865c40fcbf15d36aa65d671e
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Reaction notes

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