Cesium carbonate → HCID 89813650, compound

HRID 525349Notes

Reaction equation

HRID 525349 reaction equation
I[C:2]1[CH:20]=[CH:19][C:5]([C:6]([NH:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[N:17]=[CH:16][CH:15]=[CH:14]3)=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:69][C:70]1([CH3:83])[O:74][C:73](=[O:75])[NH:72][C@H:71]1[C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][C:77]=1[CH3:82]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:69][C:70]1([CH3:83])[O:74][C:73](=[O:75])[N:72]([C:2]2[CH:20]=[CH:19][C:5]([C:6]([NH:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]4[C:18]=3[N:17]=[CH:16][CH:15]=[CH:14]4)=[O:7])=[CH:4][CH:3]=2)[C@H:71]1[C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][C:77]=1[CH3:82]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 41661718HCID 41661718, compound2×HCID 89814050HCID 89814050, compound

Product 1

HCID 89813650HCID 89813650, compoundYield 26.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a nitrogen purged solution of 4-iodo-N-(quinolin-8-yl)benzamide (Intermediate A) (250 mg, 0.66 mmol) in 1,4-dioxane (3 mL) were added cesium carbonate (435.37 mg, 1.33 mmol), xantphos (77.31 mg, 0.13 mmol), Pd2(dba)3 (61.18 mg, 0.06 mmol) and (S)-5,5-dimethyl-4-(o-tolyl)oxazolidin-2-one (164.55 mg, 0.80 mmol). The mixture was purged with nitrogen for 5-10 minutes and then stirred for 3 hours at 100° C. After completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane), the reaction mixture was allowed to cool to ambient temperature and filtered through Celite® brand filter aid. The filtrate was concentrated and purified by column chromatography using silica gel and eluting with 30-40% EtOAc in hexane to afford (S)-4-(5,5-dimethyl-2-oxo-4-(o-tolyl)oxazolidin-3-yl)-N-(quinolin-8-yl)benzamide (80 mg, 26.51%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.55 (s, 1H), 8.95 (dd, J=4.2, 1.6 Hz, 1H), 8.68-8.66 (m, 1H), 8.46 (dd, J=8.3, 1.5 Hz, 1H), 7.97 (d, J=8.8 Hz, 2H), 7.73-7.61 (m, 5H), 7.31 (d, J=7.2 Hz, 1H), 7.23-7.15 (m, 2H), 6.96 (d, J=6.7 Hz, 1H), 5.68 (s, 1H), 1.71 (s, 3H), 0.95 (s, 3H). In CD3OD: the singlet appeared for 3H at δ 2.52 (s, 3H). m/z (ESI) 452.2 (M+H)+.

Workup

  1. customThe mixture was purged with nitrogen for 5-10 minutes
  2. customAfter completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane)
  3. temperatureto cool to ambient temperature
  4. filtrationfiltered through Celite® brand
  5. filtrationfilter aid
  6. concentrationThe filtrate was concentrated
  7. custompurified by column chromatography
  8. washeluting with 30-40% EtOAc in hexane

Sources & evidence

ORD record
ord-8794b30b6a22438395aa73552c330e9f
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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