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 1864334ノート

反応式

HRID 1864334 の反応式
[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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-b6f89a22c0b343a39a4cab911678b257
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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