Potassium Carbonate → Quinazoline

HRID 2182528Notes

Reaction equation

Cl.ClCCN1CCCC1.ClC1C=CC(N[C:16]2[C:25]3[C:20](=[CH:21][C:22](O)=[C:23](OC)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=C(F)C=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[N:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:16]=[N:17][CH:18]=1

Participants

Conditions

Temperature: 100 °C

Procedure

1-(2-Chloroethyl)pyrrolidine hydrochloride (200 mg, 1.2 mmol) was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (403 mg, 1.26 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (650 mg, 4.7 mmol) in DMF (4 ml). The mixture was heated to 100° C. and further portions of 1-(2-chloroethyl)pyrrolidine hydrochloride (800 mg in total) were added periodically over 4 hours while the reaction mixture was maintained at 100° C. The reaction was then allowed to cool and volatiles were removed by evaporation. The residue was partitioned between methylene chloride and water, separated and the organic phase passed through phase separating paper. Column chromatography eluting with methylene chloride/methanol 19/5) gave 4-(4-chloro-2-fuoroanilino)-6-methoxy-7-(pyrrolidin-1-yl)ethoxy)quinazoline (50 mg, 10%).

Workup

custom(prepared
temperaturewas maintained at 100° C
temperatureto cool
customvolatiles were removed by evaporation
customThe residue was partitioned between methylene chloride and water
customseparated
customseparating paper
washColumn chromatography eluting with methylene chloride/methanol 19/5)

Sources & evidence

ORD record: ord-4b8a17ed85b94350b6ddee120f9bd737
Source dataset: uspto-grants-2005_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06897210B2

Reaction notes

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