Morpholine → 4-(4-Fluoro-phenyl)-3-methanesulfonyl-2-methyl-6-morpholin-4-yl-quinoline

HRID 13668Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[C:13]([CH3:18])[C:12]([S:19]([CH3:22])(=[O:21])=[O:20])=[C:11]2[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>C(O)(C)(C)C.CCCCCCC.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[F:29][C:26]1[CH:27]=[CH:28][C:23]([C:11]2[C:10]3[C:15](=[CH:16][CH:17]=[C:8]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[CH:9]=3)[N:14]=[C:13]([CH3:18])[C:12]=2[S:19]([CH3:22])(=[O:21])=[O:20])=[CH:24][CH:25]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A tube placed under argon was charged with tris(dibenzylideneacetone)dipalladium chloroform complex (79 mg, 0.076 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (73 mg, 0.152 mmol) and cesium carbonate (1.86 g, 5.7 mmol). 6-Bromo-4-(4-fluoro-phenyl)-3-methanesulfonyl-2-methyl-quinoline (compound of example 14) (200 mg, 0.52 mmol) in tert.-butanol (20 ml) was added, followed by morpholine (0.40 g, 4.56 mmol). The tube was sealed and heated at 110° C. for 2 h. The reaction mixture was cooled to 20° C., diluted with heptane, filtered through dicalite and purified directly by flash chromatography on silica gel in heptane/ethyl acetate with a gradient from 100:0 to 40:60 to give a yellow solid (850 mg, 56%). MS: m/z=401 (M+H).

Workup

customA tube placed under argon
customThe tube was sealed
temperatureThe reaction mixture was cooled to 20° C.
filtrationfiltered through dicalite
custompurified directly by flash chromatography on silica gel in heptane/ethyl acetate with a gradient from 100:0 to 40:60

Sources & evidence

ORD record: ord-bd58d9fb467147b68ba15fa15a55ec0c
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728142B2

Reaction notes

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