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

HRID 1864332노트

반응식

HRID 1864332 반응식
[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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
65 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-1cdf376e78384407aa6ebb08a692ad6d
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07625908B2

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