1-Bromo-3-chloropropane → 4-(4-Chloro-2-fluoroanilino)-7-(3-chloropropoxy)-6-methoxyquinazoline

HRID 1838554Notes

Reaction equation

[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Br[CH2:24][CH2:25][CH2:26][Cl:27].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:24][CH2:25][CH2:26][Cl:27])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (957 mg, 3 mmol), (prepared as described for the starting material in Example 2), 1-bromo-3-chloropropane (2.36 g, 15 mmol) and potassium carbonate (2.1 g, 15 mmol) in DMF (20 ml) was heated at 40° C. for 1.5 hours. The mixture was allowed to cool, was diluted with water and extracted with ethyl acetate (3×50 ml). The organic extracts were combined, washed with water and brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was triturated with hexane/ethyl acetate, collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-7-(3-chloropropoxy)-6-methoxyquinazoline (650 mg, 55%).

Workup

custom(prepared
temperatureto cool
extractionextracted with ethyl acetate (3×50 ml)
washwashed with water and brine
dry with materialdried (MgSO4)
customthe volatiles were removed by evaporation
customThe residue was triturated with hexane/ethyl acetate
filtrationcollected by filtration
customdried under vacuum

Sources & evidence

ORD record: ord-5dc141a911fe4612a73ca15d77c7a8cd
Source dataset: uspto-grants-2004_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06673803B2

Reaction notes

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