Dimethylamine → N1,N2,N2-Trimethyl-N1-((2R)-2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}propyl)glycinamide

HRID 1864335ノート

反応式

HRID 1864335 の反応式
Cl[CH2:2][C:3](Cl)=[O:4].[CH3:6][C@@H:7]([O:11][C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[C:14]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]3[CH:31]=[N:32][C:33]([CH3:36])=[CH:34][CH:35]=3)=[C:25]([CH3:37])[CH:24]=1)=[N:15][CH:16]=[N:17]2)[CH2:8][NH:9][CH3:10].C[CH2:39][N:40](C(C)C)[CH:41](C)C.CNC>C(Cl)Cl.C1COCC1>[CH3:10][N:9]([CH2:8][C@H:7]([O:11][C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[C:14]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]3[CH:31]=[N:32][C:33]([CH3:36])=[CH:34][CH:35]=3)=[C:25]([CH3:37])[CH:24]=1)=[N:15][CH:16]=[N:17]2)[CH3:6])[C:3](=[O:4])[CH2:2][N:40]([CH3:41])[CH3:39]

参加物

7

反応物 4

HCID 674DimethylamineHCID 6577Chloroacetyl 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 57974367N1,N2,N2-Trimethyl-N1-((2R)-2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}propyl)glycinamide収率 41.3%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Chloroacetyl chloride (33 μl, 0.42 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 (172 mg, 0.40 mmol, obtained as described in Example 103, preparation of starting materials)) and DIPEA (139 μl, 0.8 mmol) in DCM (2 ml). The mixture was stirred at room temperature for 1 hour. THF (5 ml) was added to the solution and dimethylamine was bubbled in the reaction mixture. After 30 minutes, the solvents were evaporated under vacuum. The mixture was diluted with DCM, 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% 7N ammonia-methanol in DCM) to give the title compound (85 mg, 41%) as a pale solid; NMR spectrum (CDCl3) 1.53 (d, 3H), 2.28 (s, 6H), 2.30 (s, 3H), 2.53 (s, 3H), 3.15-3.05 (m, 5H), 3.54 (dd, 1H), 3.95 (dd, 1H), 5.10 (m, 1H), 6.91 (d, 1H), 7.12 (m, 3H), 7.46 (d, 1H), 7.55 (d, 1H), 7.64 (m, 1H), 7.72 (s, 1H), 8.27 (s, 1H), 8.62 (s, 1H); Mass spectrum: MH+ 515.

後処理

  1. customwas bubbled in the reaction mixture
  2. waitAfter 30 minutes
  3. customthe solvents were evaporated under vacuum
  4. additionThe mixture was diluted with DCM
  5. washwashed with water and brine
  6. dry with materialdried over MgSO4
  7. customAfter evaporation of the solvents
  8. customthe residue was purified by chromatography on silica gel (eluant: 2 to 4% 7N ammonia-methanol in DCM)

出典と根拠

ORDレコード
ord-67f60e7eac774461968e2af97b686615
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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