Hydrochloric Acid → N-(2-fluoro-4-methylphenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine

HRID 577376Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A suspension of 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (200 mg, 0.622 mmol), (prepared as described for the starting material in Example 2c) and 2-fluoro-4-methylaniline (94 mg, 0.764 mmol) in isopropanol (5 ml) containing 6.2M hydrogen chloride in isopropanol (110 μl) was stirred at 80° C. for 1.5 hours. After cooling, the precipitate was collected by filtration, washed with isopropanol, followed by ether and dried under vacuum. The solid was purified by column chromatography, eluting with methylene chloride/methanol (90/10) followed by 5% ammonia in methanol/methylene chloride (10/90). Evaporation of the fractions containing the expected product gave 4-(2-fluoro-4-methylanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (170 mg, 61%).

Workup

custom(prepared
temperatureAfter cooling
filtrationthe precipitate was collected by filtration
washwashed with isopropanol
customdried under vacuum
customThe solid was purified by column chromatography
washeluting with methylene chloride/methanol (90/10)
customEvaporation of the fractions
additioncontaining the expected product

Sources & evidence

ORD record: ord-1c8a08378a1c4d228876f676eb12b510
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040548B2

Reaction notes

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