Dimethylacetamide → 5-chloro-N-[3-(dimethylamino)propyl]-N-methyl-6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridine-3-sulfonamide

HRID 81671Notes

Reaction equation

HRID 81671 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]([CH2:14][CH2:15][CH2:16][N:17]([CH3:19])[CH3:18])[CH3:13])(=[O:11])=[O:10])[CH:5]=[N:6][C:7]=1Cl.CC(C)([O-])C.[K+].CN(C)C(=O)C.[CH3:32][N:33]1[CH:37]=[CH:36][C:35]([NH:38][C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[C:46]([OH:49])[CH:47]=3)[N:42]=[CH:41][N:40]=2)=[N:34]1>O>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]([CH2:14][CH2:15][CH2:16][N:17]([CH3:19])[CH3:18])[CH3:13])(=[O:11])=[O:10])[CH:5]=[N:6][C:7]=1[O:49][C:46]1[CH:47]=[C:48]2[C:43](=[CH:44][CH:45]=1)[N:42]=[CH:41][N:40]=[C:39]2[NH:38][C:35]1[CH:36]=[CH:37][N:33]([CH3:32])[N:34]=1

Participants

6

Reactant 4

HCID 31374DimethylacetamideHCID 231603824-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-olHCID 23665647Potassium tert-butoxideHCID 646088045,6-dichloro-N-[3-(dimethylamino)propyl]-N-methylpyridine-3-sulfonamide

Product 1

HCID 426110325-chloro-N-[3-(dimethylamino)propyl]-N-methyl-6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridine-3-sulfonamideYield 68%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

5,6-Dichloro-N-[3-(dimethylamino)propyl]-N-methylpyridine-3-sulfonamide (122 mg, 0.37 mmol) and potassium tert-butoxide (58 mg, 0.52 mmol) were added to an N,N-dimethylacetamide solution (1 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (50 mg, 0.21 mmol), and stirred under a nitrogen atmosphere at 100° C. for 2.5 hours. The reaction solution was cooled with ice, saline water was added, and extracted with chloroform/methanol (9:1). 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 (Biotage NH, hexane:ethyl acetate:chloroform to chloroform:methanol=2:4:1 to 100:2) to obtain the entitled compound (75 mg, yield: 68%) as a pale orange amorphous solid.

Workup

  1. additionwas added
  2. extractionextracted with chloroform/methanol (9:1)
  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 (Biotage NH, hexane:ethyl acetate:chloroform to chloroform:methanol=2:4:1 to 100:2)

Sources & evidence

ORD record
ord-7a572537e32f432ab3a81a365d3a54d5
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Reaction notes

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