1,4-Cyclohexadiene → HCID 67465629, compound

HRID 1777722Notes

Reaction equation

C([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:24]=[C:23]3[C:18]([CH:19]=[CH:20][CH:21]=[N:22]3)=[C:17]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[N:16]=2)=[C:11]([Cl:31])[CH:10]=1)C1C=CC=CC=1.C1CC=CCC=1>CCO.[OH-].[OH-].[Pd+2]>[Cl:31][C:11]1[CH:10]=[C:9]([NH2:8])[CH:14]=[CH:13][C:12]=1[C:15]1[CH:24]=[C:23]2[C:18]([CH:19]=[CH:20][CH:21]=[N:22]2)=[C:17]([N:25]2[CH2:26][CH2:27][O:28][CH2:29][CH2:30]2)[N:16]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of 4 and benzyl-[3-chloro-4-(5-morpholin-4-yl-[1,6]naphthyridin-7-yl)-phenyl]-amine (164 mg, 0.32 mmol, 1 eq) in dry EtOH (3 mL) was added Pd(OH)2 (60 mg, 40% w/w) and 1,4-cyclohexanediene (600 μL, 6.30 mmol, 20 eq) under Ar(g). The mixture was heated at 80° C. overnight. Additional quantities of Pd(OH)2 (60 mg, 40% w/w) and 1,4-cyclohexanediene (400 μL, 4.10 mmol, 15 eq) were added, and the mixture was again heated at 80° C. overnight. Once cooled down, the reaction mixture was filtered through a short celite pad, eluted with MeOH (10 mL). The solvent was removed in vacuo and the residue was further purified by silica gel column chromatography, eluting with CH2Cl2/MeOH (1:0-49:1), to furnish the product, F, as a pale yellow solid (8.1 mg, 8%).

Workup

temperaturethe mixture was again heated at 80° C. overnight
temperatureOnce cooled down
filtrationthe reaction mixture was filtered through a short celite pad
washeluted with MeOH (10 mL)
customThe solvent was removed in vacuo
customthe residue was further purified by silica gel column chromatography
washeluting with CH2Cl2/MeOH (1:0-49:1)
customto furnish the product, F

Sources & evidence

ORD record: ord-84337274b66d4a228dd45c5ab8993ca6
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266879B2

Reaction notes

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