Cesium carbonate → 3-(7-(Benzyloxy)-6-methoxyquinazolin-4-yloxy)aniline

HRID 631355Notes

Reaction equation

HRID 631355 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+].[CH2:15]([O:22][C:23]1[CH:32]=[C:31]2[C:26]([C:27](Cl)=[N:28][CH:29]=[N:30]2)=[CH:25][C:24]=1[O:34][CH3:35])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>O1CCCC1>[CH2:15]([O:22][C:23]1[CH:32]=[C:31]2[C:26]([C:27]([O:8][C:4]3[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=3)[NH2:1])=[N:28][CH:29]=[N:30]2)=[CH:25][C:24]=1[O:34][CH3:35])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 115683-AminophenolHCID 106619987-(Benzyloxy)-4-chloro-6-methoxyquinazoline

Product 1

HCID 668760933-(7-(Benzyloxy)-6-methoxyquinazolin-4-yloxy)anilineYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a stirred solution of 3-aminophenol (1.41 g, 12.93 mmol) in dry tetrahydrofuran (70 mL) at room temperature, was added cesium carbonate (6.32 g, 19.39 mmol). After stirring for a further 75 mins, added 7-(benzyloxy)-4-chloro-6-methoxyquinazoline from the previous step (3.89 g, 12.93 mmol) in one portion and the reaction mixture was heated at 75° C. for 24 h. After cooling to room temperature the mixture was concentrated under reduced pressure. The residue was partitioned between water (200 mL) and a mixture of dichloromethane (160 mL) and 2-propanol (60 mL). The mixture was filtered through a celite plug and the organic layer was separated and dried over MgSO4 and concentrated under reduced pressure. Trituration with diethyl ether, followed by filtration and drying under reduced pressure, afforded 3-(7-(benzyloxy)-6-methoxyquinazolin-4-yloxy)aniline as a cream solid (3.57 g, 74%) which was taken into the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 8.62 (s, 1H), 7.21-7.55 (m, 8H), 6.57-6.63 (m, 3H), 5.33 (s, 2H), 4.03 (s, 3H), 3.73 (brs, 2H); LC-MS (ESI) m/z 374 (M+H)+.

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. concentrationwas concentrated under reduced pressure
  3. customThe residue was partitioned between water (200 mL)
  4. additiona mixture of dichloromethane (160 mL) and 2-propanol (60 mL)
  5. filtrationThe mixture was filtered through a celite plug
  6. customthe organic layer was separated
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. filtrationTrituration with diethyl ether, followed by filtration
  10. customdrying under reduced pressure

Sources & evidence

ORD record
ord-67fa03365ece41ae8612c46fafde04ac
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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