Dimethylformamide → tert-Butyl 4-(((4-(4-amino-3-fluorophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate

HRID 387957Notes

Reaction equation

CN(C)C=O.Br[CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.C(=O)([O-])[O-].[K+].[K+].[NH2:27][C:28]1[CH:47]=[CH:46][C:31]([O:32][C:33]2[C:42]3[C:37](=[CH:38][C:39]([OH:45])=[C:40]([C:43]#[N:44])[CH:41]=3)[N:36]=[CH:35][CH:34]=2)=[CH:30][C:29]=1[F:48]>C(OCC)(=O)C.O>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][CH:8]([CH2:7][O:45][C:39]2[CH:38]=[C:37]3[C:42]([C:33]([O:32][C:31]4[CH:46]=[CH:47][C:28]([NH2:27])=[C:29]([F:48])[CH:30]=4)=[CH:34][CH:35]=[N:36]3)=[CH:41][C:40]=2[C:43]#[N:44])[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: 50 °C

Procedure

After adding dimethylformamide (4 ml), tert-butyl 4-(bromomethyl)-1-piperidine carboxylate (708 mg) and potassium carbonate (467 mg) to 4-(4-amino-3-fluorophenoxy)-6-cyano-7-hydroxyquinoline (500 mg), the mixture was heated at 50° C. for 4 hours. Water was added to the reaction solution, extraction was performed with ethyl acetate and the organic layer was washed with water and saturated saline in that order and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (n-hexane:ethyl acetate) to obtain the title compound (398 mg).

Workup

washthe organic layer was washed with water and saturated saline in that order
dry with materialdried over anhydrous sodium sulfate
distillationthe solvent was distilled off under reduced pressure
customThe obtained crude product
customwas purified by silica gel column chromatography (n-hexane:ethyl acetate)

Sources & evidence

ORD record: ord-94c552a0059042a1b505f4c91fcb52e5
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08372981B2

Reaction notes

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