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

HRID 1864332ノート

反応式

HRID 1864332 の反応式
[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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
65 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-1cdf376e78384407aa6ebb08a692ad6d
出典データセット
uspto-grants-2009_12
特許番号
US07625908B2

反応ノート

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