Sodium hydride → 5-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine

HRID 1864332Notes

Reaction equation

HRID 1864332 reaction equation
[H-].[Na+].[CH2:3]([N:6]([CH3:11])[CH2:7][C@H:8]([OH:10])[CH3:9])[CH:4]=[CH2:5].F[C:13]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:14]=1[C:15]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][C:31]3[CH:32]=[N:33][C:34]([CH3:37])=[CH:35][CH:36]=3)=[C:26]([CH3:38])[CH:25]=1)=[N:16][CH:17]=[N:18]2>C1COCC1>[CH2:3]([N:6]([CH3:11])[CH2:7][C@@H:8]([CH3:9])[O:10][C:13]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:14]=1[C:15]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][C:31]3[CH:32]=[N:33][C:34]([CH3:37])=[CH:35][CH:36]=3)=[C:26]([CH3:38])[CH:25]=1)=[N:16][CH:17]=[N:18]2)[CH:4]=[CH2:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 690241975-fluoro-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amineHCID 86615686(2R)-1-[allyl(methyl)amino]propan-2-ol

Product 1

HCID 690578815-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amineYield 51.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Sodium hydride (960 mg, 60% dispersion in oil, 20 mmol) was added portion wise to an ice-cooled solution of (2R)-1-[allyl(methyl)amino]propan-2-ol (3.87 g, 30 mmol, obtained as described in Example 2.3, preparation of starting materials) and 5-fluoro-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine (3.6 g, 10 mmol) in THF (25 ml). The mixture was heated at 65° C. for 24 hours. After cooling, the solvents were evaporated under vacuum. The mixture was diluted with DCM, and washed with water and brine. The organic layer was dried over MgSO4. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 2 to 4% methanol in DCM) to give 5-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine (2.4 g, 51%) as a brown oil; Mass spectrum: MH+ 470.

Workup

  1. temperatureAfter cooling
  2. customthe solvents were evaporated under vacuum
  3. additionThe mixture was diluted with DCM
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. customAfter evaporation of the solvents
  7. customthe residue was purified by chromatography on silica gel (eluant: 2 to 4% methanol in DCM)

Sources & evidence

ORD record
ord-1cdf376e78384407aa6ebb08a692ad6d
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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