Water → 4-(4-Chloro-2-fluorophenylamino)-7-(2,3-epoxypropoxy)-6-methoxyquinazoline

HRID 1372990Notes

Reaction equation

[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[F:20])=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:21][CH3:22].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH:31]1[O:33][CH2:32]1.O>CN(C=O)C>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:6]2[C:5]3[C:10](=[CH:11][C:2]([O:1][CH2:30][CH:31]4[O:33][CH2:32]4)=[C:3]([O:21][CH3:22])[CH:4]=3)[N:9]=[CH:8][N:7]=2)=[C:14]([F:20])[CH:15]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 7-hydroxy-6-methoxy-4-(2-fluoro-4-chlorophenylamino)quinazoline (5.56 g, 17.4 mmol) in DMF (100 ml) containing potassium carbonate (4.8 g, 34.8 mmol) was added 1-bromo-2,3-epoxypropane (1.49 ml, 17.4 mmol). The mixture was stirred at 60° C. for 3 hours. After cooling, water (400 ml) was added The precipitate was filtered and dried under vacuum at 60° C. for 2 hours over P2O5. The product was purified by column chromatography eluting with methylene chloride followed by methylene chloride/methanol saturated with ammonia 98/2. The fractions containing the expected product were combined and evaporated to give 4-(4-chloro-2-fluorophenylamino)-7-(2,3-epoxypropoxy)-6-methoxyquinazoline (2.82 g, 43%).

Workup

temperatureAfter cooling
filtrationwas filtered
dry with materialdried under vacuum at 60° C. for 2 hours over P2O5
customThe product was purified by column chromatography
washeluting with methylene chloride
additionThe fractions containing the expected product
customevaporated

Sources & evidence

ORD record: ord-d9979da0bb3146589e01f1d62ba6c902
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07160889B2

Reaction notes

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