4-Aminophenol → 4-(6,7-Dimethoxyquinazolin-4-yloxy)aniline

HRID 2272739Notes

Reaction equation

ClC1C2C(=CC(OC)=C(OC)C=2)N=CN=1.[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[O:28][CH3:29])[N:24]=[CH:23][N:22]=[C:21]2[O:30][C:31]1[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][CH:32]=1.NC1C=CC(O)=CC=1.CC(=O)CC.[OH-].[Na+]>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].C(Cl)Cl>[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[O:28][CH3:29])[N:24]=[CH:23][N:22]=[C:21]2[O:30][C:31]1[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][CH:32]=1

Participants

Conditions

Temperature: 80 °C

Procedure

4-(6,7-Dimethoxy-quinazolin-4-yloxy)-phenylamine 4-Chloro-6,7-dimethoxy-quinazoline (0.500 g, 2.22 mmol), 4-aminophenol (0.291 g, 2.67 mmol), 2-butanone (4.01 mL, 44.5 mmol), 2N sodium hydroxide solution (1.00 mL, 0.213 mmol), and tetra-N-butylammonium bromide (0.308 g, 0.957 mmol) were combined and heated to reflux (80° C.) for 15 min. The reaction was cooled to rt. DCM was added and washed with calcium carbonate solution and brine, then dried over sodium sulfate and concentrated to yield a crude product. The solid was triturated with diethyl ether and hexanes to yield 4-(6,7-dimethoxyquinazolin-4-yloxy)-phenylamine (0.52 g, 78%). LCMS m/z=298 (M+1).

Workup

temperatureheated
temperatureThe reaction was cooled to rt
washwashed with calcium carbonate solution and brine
dry with materialdried over sodium sulfate
concentrationconcentrated
customto yield a crude product
customThe solid was triturated with diethyl ether and hexanes

Sources & evidence

ORD record: ord-f0237a181a8e40c480f9344f6d6e1074
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120778B2

Reaction notes

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