Dimethyl Sulfoxide → 6-{[5-((1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-3-chloropyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine

HRID 1517304Notes

Reaction equation

HRID 1517304 reaction equation
CS([O:5][C@@H:6]([CH3:16])[CH2:7][O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])(=O)=O.CC(C)([O-])C.[K+].CS(C)=O.[Cl:27][C:28]1[CH:29]=[C:30](O)[CH:31]=[N:32][C:33]=1[O:34][C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[N:41]=[CH:40][N:39]=[C:38]2[NH:45][C:46]1[CH:50]=[CH:49][N:48]([CH3:51])[N:47]=1>O>[Si:9]([O:8][CH2:7][C@@H:6]([CH3:16])[O:5][C:30]1[CH:29]=[C:28]([Cl:27])[C:33]([O:34][C:35]2[CH:36]=[C:37]3[C:42](=[CH:43][CH:44]=2)[N:41]=[CH:40][N:39]=[C:38]3[NH:45][C:46]2[CH:50]=[CH:49][N:48]([CH3:51])[N:47]=2)=[N:32][CH:31]=1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 23665647Potassium tert-butoxideHCID 684297045-chloro-6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-olHCID 86645903(S)-1-[(tert-Butyldimethylsilyl)oxy]propan-2-yl Methanesulfonate

Product 1

HCID 684307036-{[5-((1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-3-chloropyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amineYield 33.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

(1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl methanesulfonate (79 mg, 0.29 mmol) and potassium tert-butoxide (55 mg, 0.49 mmol) were added to a dimethyl sulfoxide solution (3 ml) of 5-chloro-6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol (90 mg, 0.24 mmol) obtained in Example 22, then stirred for 24 hours at 100° C. The reaction solution was cooled to room temperature, water was added, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2 to 0:1) to obtain 6-{[5-((1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-3-chloropyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine (43 mg, yield: 33%) as a white solid.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated saline water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2 to 0:1)

Sources & evidence

ORD record
ord-72a91da84ab34c9c86e7c54e29b527e6
Source dataset
uspto-grants-2012_07
Patent number
US08232284B2

Reaction notes

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