Potassium Iodide → 6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-{[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]methoxy}quinazoline

HRID 1668675Notes

Reaction equation

Cl[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][CH:8]([CH2:11][O:12][C:13]2[CH:22]=[C:21]3[C:16]([C:17]([O:23][C:24]4[CH:25]=[C:26]5[C:30](=[CH:31][CH:32]=4)[NH:29][CH:28]=[C:27]5[CH3:33])=[N:18][CH:19]=[N:20]3)=[CH:15][C:14]=2[O:34][CH3:35])[CH2:7][CH2:6]1)=[O:4].[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1.[I-].[K+]>CN(C=O)C>[CH3:35][O:34][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:13]=1[O:12][CH2:11][CH:8]1[CH2:9][CH2:10][N:5]([C:3](=[O:4])[CH2:2][N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH2:6][CH2:7]1)[N:20]=[CH:19][N:18]=[C:17]2[O:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][CH:28]=[C:27]2[CH3:33]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 7-{[1-(chloroacetyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline (0.118 g), pyrrolidine (0.059 ml), potassium iodide (0.01 g) and DMF (3 ml) was stirred and heated to 80° C. for 40 minutes. The mixture was cooled to ambient temperature, the solvent was removed by evaporation under vacuum and the residue was purified by column chromatography on silica using increasingly polar solvent mixtures, starting with dichloromethane and ending dichloromethane/methanol saturated with ammonia (3.5M) (94/6). Evaporation of the solvents gave a foam which was triturated under ether/pentane (70/30) to give a solid which was collected by filtration and dried under vacuum to give 6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-{[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]methoxy}quinazoline (0.096 g).

Workup

temperatureThe mixture was cooled to ambient temperature
customthe solvent was removed by evaporation under vacuum
customthe residue was purified by column chromatography on silica using
temperatureincreasingly polar solvent mixtures
customEvaporation of the solvents
customgave a foam which
customwas triturated under ether/pentane (70/30)
customto give a solid which
filtrationwas collected by filtration
customdried under vacuum

Sources & evidence

ORD record: ord-2100e3c2c3854df9aabd9a30749158f1
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989460B2

Reaction notes

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