Dimethylformamide → 2-(2-Phenyl-1,3-dioxan-5-yl)oxy-4-(3,4-methylenedioxybenzyl)amino-6-chloroquinazoline

HRID 2392882Notes

Reaction equation

[H-].[Na+].[OH:3][CH:4]1[CH2:9][O:8][CH:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:6][CH2:5]1.CN(C)C=O.Cl[C:22]1[N:31]=[C:30]([NH:32][CH2:33][C:34]2[CH:39]=[CH:38][C:37]3[O:40][CH2:41][O:42][C:36]=3[CH:35]=2)[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([Cl:43])[CH:28]=2)[N:23]=1>O>[C:10]1([CH:7]2[O:6][CH2:5][CH:4]([O:3][C:22]3[N:31]=[C:30]([NH:32][CH2:33][C:34]4[CH:39]=[CH:38][C:37]5[O:40][CH2:41][O:42][C:36]=5[CH:35]=4)[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([Cl:43])[CH:28]=4)[N:23]=3)[CH2:9][O:8]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

Conditions

Temperature: 80 °C

Procedure

100 mg of sodium hydride was added to a mixture comprising 300 mg of 5-hydroxy-2-phenyl-1,3-dioxane and 5 ml of dimethylformamide. The obtained mixture was heated to 80° C. After the bubbling had been discontinued, 300 mg of 2,6-dichloro-4-(3,4-methylenedioxybenzyl)aminoquinazoline was added in a crystalline state. The obtained mixture was heated at 140° C. for 2 hours and cooled, followed by the addition of water. The obtained mixture was extracted with ethyl acetate. The extract was purified by silica gel column chromatography using an ethyl acetate/benzene mixture to give 118 mg of 2-(2-phenyl-1,3-dioxan-5-yl)oxy-4-(3,4-methylenedioxybenzyl)amino-6-chloroquinazoline. 100 mg of this compound was hydrolyzed with concentrated hydrochloric acid/ethanol by a conventional process to give 60 mg of the title compound through rearrangement.

Workup

temperatureThe obtained mixture was heated at 140° C. for 2 hours
temperaturecooled
extractionThe obtained mixture was extracted with ethyl acetate
customThe extract was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-aa85e06b8c044c8eb39b7f5dc5eb0a24
Source dataset: uspto-grants-1998_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05801180

Reaction notes

Loading…