Dimethylacetamide → 6-({3-chloro-5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridin-2-yl}oxy)-N-(5-methylpyrazin-2-yl)quinazoline-4-amine

HRID 1517293Notes

Reaction equation

HRID 1517293 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[C:9](F)=[N:10][CH:11]=[C:12]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH:13]=1.CN(C)C(=O)C.[CH3:32][C:33]1[N:34]=[CH:35][C:36]([NH:39][C:40]2[C:49]3[C:44](=[CH:45][CH:46]=[C:47]([OH:50])[CH:48]=3)[N:43]=[CH:42][N:41]=2)=[N:37][CH:38]=1>O>[Cl:7][C:8]1[C:9]([O:50][C:47]2[CH:48]=[C:49]3[C:44](=[CH:45][CH:46]=2)[N:43]=[CH:42][N:41]=[C:40]3[NH:39][C:36]2[CH:35]=[N:34][C:33]([CH3:32])=[CH:38][N:37]=2)=[N:10][CH:11]=[C:12]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH:13]=1

Participants

6

Reactant 4

HCID 31374DimethylacetamideHCID 23665647Potassium tert-butoxideHCID 684297613-chloro-2-fluoro-5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridineHCID 1356182224-((5-Methylpyrazin-2-yl)amino)quinazolin-6-ol

Product 1

HCID 684277076-({3-chloro-5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridin-2-yl}oxy)-N-(5-methylpyrazin-2-yl)quinazoline-4-amineYield 71%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
180 °C

Procedure

Potassium tert-butoxide (0.89 g, 7.90 mmol) and 3-chloro-2-fluoro-5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridine (2.52 g, 8.69 mmol) were added to an N,N-dimethylacetamide solution (2.5 ml) of 4-[(5-methylpyrazin-2-yl)amino]quinazolin-6-ol (1.0 g, 3.95 mmol), and stirred at 180° C. for 14 hours under a nitrogen atmosphere in a sealed tube. The reaction solution was cooled with ice, water was added, and extracted with chloroform/methanol (10:1). The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by amine-type silica gel column chromatography (Moritex NH, hexane:ethyl acetate=3:1 to 3:2) to obtain 6-({3-chloro-5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridin-2-yl}oxy)-N-(5-methylpyrazin-2-yl)quinazoline-4-amine (1.46 g, yield: 71%) as an orange oil.

Workup

  1. additionwas added
  2. extractionextracted with chloroform/methanol (10:1)
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by amine-type silica gel column chromatography (Moritex NH, hexane:ethyl acetate=3:1 to 3:2)

Sources & evidence

ORD record
ord-a1bdef4c2974407db5066a33a4187a59
Source dataset
uspto-grants-2012_07
Patent number
US08232284B2

Reaction notes

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