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

HRID 2227936Notes

Reaction equation

[Br: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>[Br: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: 45 °C

Procedure

A mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (1.2 g, 3.3 mmol), (prepared as described for the starting material in Example 48), 1-bromo-3-chloropropane (1.6 ml, 16 mmol) and potassium carbonate (2.1 g, 15 mmol) in DMF (25 ml) was heated at 45° C. for 3 hours. The mixture was allowed to cool, was diluted with water and extracted with ethyl acetate (3×70 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 hexantlethyl acetate, collected by filtration and dried under vacuum to give 4-(4-bromo-2-fluoroanihno)-7-(3-chloropropoxy)-6-methoxyquinazoline (492 mg, 34%).

Workup

custom(prepared
temperatureto cool
extractionextracted with ethyl acetate (3×70 ml)
washwashed with water and brine
dry with materialdried (MgSO4)
customthe volatiles were removed by evaporation
customThe residue was triturated with hexantlethyl acetate
filtrationcollected by filtration
customdried under vacuum

Sources & evidence

ORD record: ord-fe9b6d92a37a4f9b9fc2d2dea27ec3e2
Source dataset: uspto-grants-2002_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06414148B1

Reaction notes

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