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

HRID 1433616Notes

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 brine 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 brine 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-268b2a69e45641d19e202ad3cf4ef47f
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612092B2

Reaction notes

Loading…