3-Methyl-4-((6-methylpyridin-3-yl)oxy)aniline → N-methyl-N-(2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}ethyl)acetamide

HRID 1864354ノート

反応式

HRID 1864354 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][CH2:14][N:15]([CH3:19])[C:16](=[O:18])[CH3:17])[N:5]=[CH:4][N:3]=1.[CH3:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[O:28][C:29]1[CH:30]=[N:31][C:32]([CH3:35])=[CH:33][CH:34]=1)[NH2:24]>C(O)(C)C>[CH3:19][N:15]([CH2:14][CH2:13][O:12][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[C:2]([NH:24][C:23]1[CH:25]=[CH:26][C:27]([O:28][C:29]3[CH:30]=[N:31][C:32]([CH3:35])=[CH:33][CH:34]=3)=[C:21]([CH3:20])[CH:22]=1)=[N:3][CH:4]=[N:5]2)[C:16](=[O:18])[CH3:17]

参加物

4

反応物 2

HCID 114244343-Methyl-4-((6-methylpyridin-3-yl)oxy)anilineHCID 86615689N-{2-[(4-Chloroquinazolin-5-yl)oxy]ethyl}-N-methylacetamide

生成物 1

HCID 11408478N-methyl-N-(2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}ethyl)acetamide

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

N-{2-[(4-Chloroquinazolin-5-yl)oxy]ethyl}-N-methylacetamide (38 mg, 0.136 mmol) and 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (obtained as described in Example 103, preparation of stating materials, 32 mg, 0.150 mmol) were dissolved in iso-propanol, and the mixture heated to reflux for 1 hour. The mixture was concentrated in vacuo, and the residue purified by chromatography, eluting with 0 to 5.5% (10:1 methanol/conc. NH3(aq)) in ethyl acetate. Evaporation of the appropriate fractions gave N-methyl-N-(2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}ethyl)acetamide as a dry film (24 mg, 39%); NMR Spectrum (DMSO-d6, 400 MHz), 373K 1.96 (s, 3H), 2.24 (s, 3H), 2.46 (s, 3H), 2.94 (s, 3H), 3.90 (t, 2H), 4.50 (t, 3H), 6.94 (d, 1H), 7.18 (d, 1H), 7.21 (m, 2H), 7.36 (d, 1H), 7.63 (dd, 1H), 7.68 (d, 1H), 7.71 (dd, 1H), 8.17 (dd, 1H), 8.47 (s, 1H), 9.76 (s, 1H); Mass spectrum MH+ 458.4.

後処理

  1. temperaturethe mixture heated
  2. temperatureto reflux for 1 hour
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue purified by chromatography
  5. washeluting with 0 to 5.5% (10:1 methanol/conc. NH3(aq)) in ethyl acetate
  6. customEvaporation of the appropriate fractions

出典と根拠

ORDレコード
ord-e4e2e078ccca4b399a03a21f5b25ab14
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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