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 1864354Notes

Reaction equation

HRID 1864354 reaction equation
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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-e4e2e078ccca4b399a03a21f5b25ab14
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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