HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

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 81665
Notes
Print preview

Reaction equation

HRID 81665 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

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 68430703
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
Yield 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-610484f303da462f928cb2c41e0de7dd
Source dataset
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08846700B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes