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 1864354노트

반응식

HRID 1864354 반응식
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]

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-e4e2e078ccca4b399a03a21f5b25ab14
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07625908B2

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