Hydrochloric Acid → 4-(3-Chloro-2,4-difluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline

HRID 1879952Notes

Reaction equation

[Cl:1][C:2]1[C:3]([F:10])=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:37][CH3:38])=[C:20]([O:23][CH:24]3[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]3)[CH:21]=2)[N:16]=[CH:15][N:14]=1>C(O)(C)C>[Cl:1][C:2]1[C:3]([F:10])=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH:5][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:37][CH3:38])=[C:20]([O:23][CH:24]3[CH2:25][CH2:26][NH:27][CH2:28][CH2:29]3)[CH:21]=2)[N:16]=[CH:15][N:14]=1

Participants

Conditions

Temperature: 80 °C

Procedure

3-Chloro-2,4-difluoroaniline (1.7 g, 10.1 mmol) and 5N hydrogen chloride in isopropanol (2 ml) were added to a suspension of tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylate (4 g, 10.1 mmol, PCT Int. Appl. WO2003082831, AstraZeneca) in isopropanol (50 ml). The mixture was stirred at 80° C. for 3 hours. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 5-10% 7N methanolic ammonia in dichloromethane) to give 4-(3-chloro-2,4-difluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline (3.63 g, 85%) as a white solid.

Workup

customAfter evaporation of the solvents
customthe residue was purified by chromatography on silica gel (eluant: 5-10% 7N methanolic ammonia in dichloromethane)

Sources & evidence

ORD record: ord-10051745993244af99cbce89c78a3b41
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318752B2

Reaction notes

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