Potassium Iodide → 6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]-7-[2-(tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrol-5-yl)ethoxy]quinazoline

HRID 1668677Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 7-(2-chloroethoxy)-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazoline (0.15 g), tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyrrole hydrochloride (0.10 g), potassium carbonate (0.09 g) and potassium iodide (0.1 g) in DMA (1.5 ml) was stirred and heated at 80° C. for 12 hours. The mixture was diluted in DMF (0.8 ml), filtrated and purified by preparative LCMS (Hypersil C18-13-Basic column using a solvent gradient consisting of acetonitrile and water buffered with a 5% ammonium carbonate solution (100 g/L, pH 8.9). The solvent was removed by evaporation under vacuum and the residue was triturated under diethyl ether, filtered and dried to give 6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]-7-[2-(tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrol-5-yl)ethoxy]quinazoline (0.10 g) as a pale yellow solid.

Workup

filtrationfiltrated
custompurified by preparative LCMS (Hypersil C18-13-Basic column
customThe solvent was removed by evaporation under vacuum
customthe residue was triturated under diethyl ether
filtrationfiltered
customdried

Sources & evidence

ORD record: ord-b239d336cef44c00bc90e368f72e39e4
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989460B2

Reaction notes

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