Acetyl chloride → N-Methyl-N-((2R)-2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}propyl)acetamide

HRID 1864334노트

반응식

HRID 1864334 반응식
[C:1](Cl)(=[O:3])[CH3:2].[CH3:5][C@@H:6]([O:10][C:11]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:12]=1[C:13]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]3[CH:30]=[N:31][C:32]([CH3:35])=[CH:33][CH:34]=3)=[C:24]([CH3:36])[CH:23]=1)=[N:14][CH:15]=[N:16]2)[CH2:7][NH:8][CH3:9].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:9][N:8]([CH2:7][C@H:6]([O:10][C:11]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:12]=1[C:13]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]3[CH:30]=[N:31][C:32]([CH3:35])=[CH:33][CH:34]=3)=[C:24]([CH3:36])[CH:23]=1)=[N:14][CH:15]=[N:16]2)[CH3:5])[C:1](=[O:3])[CH3:2]

참가 물질

5

반응물 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 690612485-[(1R)-1-methyl-2-(methylamino)ethoxy]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine

생성물 1

HCID 57974347N-Methyl-N-((2R)-2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}propyl)acetamide수율 60%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

Acetyl chloride (24 μl, 0.33 mmol) was added drop wise to a solution of 5-[(1R)-1-methyl-2-(methylamino)ethoxy]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine (129 mg, 0.30 mmol, obtained as described in Example 103, preparation of starting materials) and DIPEA (105 μl, 0.6 mmol) in DCM (5 ml). The mixture was stirred at room temperature for 2 hours and diluted with DCM. The solution was washed with water and brine, and 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 the title compound (84 mg, 60%) as a pale solid; NMR spectrum (CDCl3) 1.55 (d, 3H), 2.08 (s, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 3.08 (s, 3H), 3.56 (dd, 1H), 3.93 (dd, 1H), 5.09 (m, 1H), 6.92 (d, 1H), 7.12 (m, 3H), 7.50 (m, 2H), 7.65 (m, 1H), 7.70 (s, 1H), 8.27 (s, 1H), 8.62 (s, 1H); Mass spectrum: MH+ 472.

후처리

  1. washThe solution was washed with water and brine
  2. dry with materialdried over MgSO4
  3. customAfter evaporation of the solvents
  4. customthe residue was purified by chromatography on silica gel (eluant: 2 to 4% methanol in DCM)

출처 및 근거

ORD 기록
ord-b6f89a22c0b343a39a4cab911678b257
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07625908B2

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