4-Chloro-6,7-dimethoxyquinoline → 5-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-N-phenylpyrimidin-2-amine

HRID 1993355Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[F:16][C:17]1[CH:22]=[C:21]([C:23]2[CH:24]=[N:25][C:26]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[N:27][CH:28]=2)[CH:20]=[CH:19][C:18]=1[OH:36]>O1CCOCC1.N1C=CC=CC=1.CN(C1C=CN=CC=1)C.[OH-].[Na+]>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][CH:3]=[C:2]2[O:36][C:18]1[CH:19]=[CH:20][C:21]([C:23]2[CH:24]=[N:25][C:26]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[N:27][CH:28]=2)=[CH:22][C:17]=1[F:16]

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of 4-chloro-6,7-dimethoxyquinoline (0.064 g, 0.28 mmol) and 2-fluoro-4-(2-(phenylamino)pyrimidin-5-yl)phenol (Step 3, 0.48 g, 0.17 mmol) in dioxane (1.0 mL) and pyridine (0.5 mL) was treated with a catalytic amount of DMAP (0.12 g, 0.1 mmol). The mixture was heated under microwave irradiation at 180° C. for 30 min. After cooling to RT, the mixture was diluted with NaOH (0.2 N, 6 mL), and the suspension was filtered. The resulting solid was further purified on silica with 0-5% (NH3-MeOH in DCM) to afford the title compound as a white solid. MS (ESI pos. ion) m/z: 469. Calc'd for C27H21FN4O3: 468.16.

Workup

temperatureAfter cooling to RT
filtrationthe suspension was filtered
customThe resulting solid was further purified on silica with 0-5% (NH3-MeOH in DCM)

Sources & evidence

ORD record: ord-8dd05aeec77b401c97f3775da911c88d
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652009B2

Reaction notes

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