Cesium carbonate → 3-(6-Methoxy-7-(2-morpholinoethoxy)quinazolin-4-yloxy)aniline

HRID 631563Notes

Reaction equation

HRID 631563 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH2:30][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1>C(O)(C)C>[CH3:27][O:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][C:22]=1[O:28][CH2:29][CH2:30][N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)[N:19]=[CH:18][N:17]=[C:16]2[O:8][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[NH2:1]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 115683-AminophenolHCID 108710274-Chloro-6-methoxy-7-(2-morpholinoethoxy)quinazoline

Product 1

HCID 668766313-(6-Methoxy-7-(2-morpholinoethoxy)quinazolin-4-yloxy)anilineYield 22%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

3-Aminophenol (338 mg, 3.09 mmol) was treated with cesium carbonate (2 g, 6.2 mmol) in anhydrous isopropanol (10 mL) and the mixture stirred at room temperature for 30 minutes. 4-(2-(4-chloro-6-methoxyquinazolin-7-yloxy)ethyl)morpholine from the previous step (1 g, 3.09 mmol) was added and the mixture stirred at 80° C. for 2h. Cesium carbonate was filtered off, washed with isopropanol and the filtrate concentrated under reduced pressure. The residue was purified by silica gel chromatography (dichloromethane/methanol 9:1) to afford 3-(6-methoxy-7-(2-morpholinoethoxy)quinazolin-4-yloxy)aniline (236 mg, 22%) as a browish solid. 1H NMR (300 MHz, DMSO-d6) δ 8.54 (s, 1H), 7.51 (s, 1H), 7.41 (s, 1H), 7.09 (t, 1H), 6.50-6.37 (m, 3H), 5.30 (bs, 2H), 4.34-4.30 (m, 2H), 3.91 (s, 3H), 3.60 (s, 4H), 2.82-2.70 (m, 2H) 2.59-2.42 (m, 4H); LC-MS (ESI) m/z 397 (M+H)+.

Workup

  1. stirringthe mixture stirred at 80° C. for 2h
  2. filtrationCesium carbonate was filtered off
  3. washwashed with isopropanol
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (dichloromethane/methanol 9:1)

Sources & evidence

ORD record
ord-fc3978d7386e4dfd895390b9b9314ced
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

Loading…