Hydrochloric Acid → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline hydrochloride

HRID 577373Notes

Reaction equation

Cl.C(O)C.[Cl:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH2:19][CH:20]3[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]3)=[C:13]([O:16][CH3:17])[CH:14]=2)[N:9]=[CH:8][N:7]=1.[Cl:27][C:28]1[CH:34]=[CH:33][C:31]([NH2:32])=[C:30]([F:35])[CH:29]=1>C(O)(C)C.CCOCC>[ClH:5].[Cl:27][C:28]1[CH:34]=[CH:33][C:31]([NH:32][C:6]2[C:15]3[C:10](=[CH:11][C:12]([O:18][CH2:19][CH:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)=[C:13]([O:16][CH3:17])[CH:14]=3)[N:9]=[CH:8][N:7]=2)=[C:30]([F:35])[CH:29]=1

Participants

Conditions

Temperature: 50 °C

Procedure

3.5M Hydrogen chloride in ethanol (75 μl, 0.26 mmol) was added to a suspension of 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (80 mg, 0.25 mmol), (prepared as described for the starting material in Example 2c), in isopropanol (3 ml), the mixture was heated to 50° C. and 4-chloro-2-fluoroaniline (44 mg, 0.3 mmol) was added. The mixture was heated at reflux for 30 minutes. After cooling, the mixture was diluted with ether (3 ml). The precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline hydrochloride (105 mg, 82%).

Workup

custom(prepared
temperatureThe mixture was heated
temperatureat reflux for 30 minutes
temperatureAfter cooling
filtrationThe precipitate was collected by filtration
washwashed with ether
customdried under vacuum

Sources & evidence

ORD record: ord-e2835a4cd59e4fa08be8f9725789d1dc
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040548B2

Reaction notes

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