Potassium Carbonate → 4-(6-Fluoroindol-5-yloxy)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline

HRID 454231Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:23][C:24]1[CH:32]=[C:31]2[C:27]([CH:28]=[CH:29][NH:30]2)=[CH:26][C:25]=1[OH:33].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:23][C:24]1[CH:32]=[C:31]2[C:27]([CH:28]=[CH:29][NH:30]2)=[CH:26][C:25]=1[O:33][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 95 °C

Procedure

A solution of 4-chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (213 mg, 0.662 mmol), (prepared as described for the starting material in Example 10), and 6-fluoro-5-hydroxyindole (120 mg, 0.794 mmol) in DMF (3 ml) containing potassium carbonate (137 mg, 0.994 mmol) was stirred at 95° C. for 3.5 hours. After cooling, the mixture was poured onto water. The mixture was filtered and the solid was washed with water. The solid was dissolved in methylene chloride. The organic layer was dried (MgSO4), and evaporated. The residue was triturated with ether/ethyl acetate and the solid was filtered and dried under vacuum to give 4-(6-fluoroindol-5-yloxy)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (135 mg, 46%).

Workup

temperatureAfter cooling
additionthe mixture was poured onto water
filtrationThe mixture was filtered
washthe solid was washed with water
dissolutionThe solid was dissolved in methylene chloride
dry with materialThe organic layer was dried (MgSO4)
customevaporated
customThe residue was triturated with ether/ethyl acetate
filtrationthe solid was filtered
customdried under vacuum

Sources & evidence

ORD record: ord-376b24dcb3b14127be3af6db2d8c43e7
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08492560B2

Reaction notes

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