Water → 5-(6,7-Dimethoxyquinazolin-4-yloxy)-2,4-difluoroaniline

HRID 631595Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[C:9]([F:16])=[CH:10][C:11]([F:15])=[C:12]([OH:14])[CH:13]=1.Cl[C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH3:31])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.O>CN(C=O)C>[CH3:29][O:28][C:25]1[CH:26]=[C:27]2[C:22](=[CH:23][C:24]=1[O:30][CH3:31])[N:21]=[CH:20][N:19]=[C:18]2[O:14][C:12]1[C:11]([F:15])=[CH:10][C:9]([F:16])=[C:8]([CH:13]=1)[NH2:7]

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred suspension of cesium carbonate (3.25 g, 10.0 mmoles) in dry DMF (20 mL) was added 5-amino-2,4-difluorophenol (1.00 g, 6.9 mmoles). This solution was heated to 80° C. for 1 hour, and 4-chloro-6,7-dimethoxyquinazoline (1.59 g, 7.1 mmoles) was added and the reaction heated for an additional hour. At the end of this time the reaction was poured into water (200 mL) and extracted with two portions (200 mL) of ethyl acetate. The extracts were combined and dried over MgSO4. Filtration and concentration afforded 5-(6,7-dimethoxyquinazolin-4-yloxy)-2,4-difluoroaniline as a crude red oil. Purification by silica gel chromatography eluting with an ethyl acetate/hexane gradient, 30%-70% over 70 minutes gave a slightly impure oil containing DMF. This oil was crystallized using ethyl acetate hexane to give a white solid.

Workup

temperaturethe reaction heated for an additional hour
extractionextracted with two portions (200 mL) of ethyl acetate
dry with materialdried over MgSO4
filtrationFiltration and concentration

Sources & evidence

ORD record: ord-12c135d3b6d0458e9cbdd636411c546c
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09320739B2

Reaction notes

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