Morpholine → 3-Methanesulfonyl-2-methyl-6-morpholin-4-yl-4-(2,4,5-trifluoro-phenyl)-quinoline

HRID 13672Notes

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]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:24]=1[F:31].[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]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>[CH3:22][S:19]([C:12]1[C:13]([CH3:18])=[N:14][C:15]2[C:10]([C:11]=1[C:23]1[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:24]=1[F:31])=[CH:9][C:8]([N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1)=[CH:17][CH:16]=2)(=[O:21])=[O:20]

Participants

Conditions

Temperature: 110 °C

Procedure

A tube placed under argon was charged with tris(dibenzylideneacetone)dipalladium chloroform complex (19 mg, 0.019 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (18 mg, 0.019 mmol) and cesium carbonate (454 mg, 1.4 mmol). 6-Bromo-3-methanesulfonyl-2-methyl-4-(2,4,5-trifluoro-phenyl)-quinoline (compound of example 21) (400 mg, 0.93 mmol) in tert.-butanol (20 ml) was added, followed by morpholine (97 mg, 1.11 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 100:0 to 40:60 to give a yellow solid (250 mg, 62%). MS: m/z=437 (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 100:0 to 40:60

Sources & evidence

ORD record: ord-fb53ae19de0e4d1dbb783d79a84938b2
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728142B2

Reaction notes

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