Cesium carbonate → HCID 89814065, compound

HRID 525358Notes

Reaction equation

HRID 525358 reaction equation
[C:1]1([CH:7]2[C:11]3([CH2:14][CH2:13][CH2:12]3)[O:10][C:9](=[O:15])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:17]1[CH:35]=[CH:34][C:20]([C:21]([NH:23][C:24]2[CH:25]=[CH:26][CH:27]=[C:28]3[C:33]=2[N:32]=[CH:31][CH:30]=[CH:29]3)=[O:22])=[CH:19][CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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]>[O:15]=[C:9]1[N:8]([C:17]2[CH:35]=[CH:34][C:20]([C:21]([NH:23][C:24]3[CH:25]=[CH:26][CH:27]=[C:28]4[C:33]=3[N:32]=[CH:31][CH:30]=[CH:29]4)=[O:22])=[CH:19][CH:18]=2)[CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:11]2([CH2:14][CH2:13][CH2:12]2)[O:10]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 41661718HCID 41661718, compoundHCID 89813956HCID 89813956, compound

Product 1

HCID 89814065HCID 89814065, compoundYield 12%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

A mixture of 8-phenyl-5-oxa-7-azaspiro[3.4]octan-6-one (0.3 g, 1.57 mmol), 4-iodo-N-(quinolin-8-yl)benzamide, (0.650 g, 1.73 mmol), Cs2CO3 (1.125 g, 3.47 mmol), X-Phos (40 mg, 0.07 mmol) and Pd2(dba)3 (73 mg, 0.07 mmol) in 1,4-dioxane (2 mL) in a 50 mL round bottom flask was purged with N2 gas for 15 minutes. The reaction mixture was then heated at 90° C. for 12 hours. After completion of reaction (monitored by TLC, TLC eluent: 30% EtOAc in hexane), the reaction mixture was cooled, and 1,4-dioxane was evaporated under reduced pressure to afford initial product. The initial product was purified by column chromatography using silica gel eluting with 20% EtOAc in hexane to yield (R+S) 4-(6-oxo-8-phenyl-5-oxa-7-azaspiro[3.4]octan-7-yl)-N-(quinolin-8-yl)benzamide (70 mg, 12%) as a brown solid. 1H NMR (400 MHz, CDCl3) δ: 10.65 (s, 1H), 8.88 (dd, J=7.2, 1.6 Hz, 1H), 8.83-8.81 (m, 1H), 8.18 (dd, J=8.4, 1.6 Hz, 1H), 7.99-7.96 (m, 2H), 7.67-7.64 (m, 2H), 7.59-7.51 (m, 2H), 7.49-7.45 (m, 1H), 7.43-7.34 (m, 3H), 7.29-7.26 (m, 2H), 5.23 (s, 1H), 2.68-2.63 (m, 1H), 2.48-2.43 (m, 1H), 2.22-2.18 (m, 1H), 1.96-1.91 (m, 1H), 1.76-1.71 (m, 1H), 1.62-1.57 (m, 1H). m/z (ESI) 450.1 (M+H)+.

Workup

  1. customwas purged with N2 gas for 15 minutes
  2. customAfter completion of reaction (monitored by TLC, TLC eluent: 30% EtOAc in hexane)
  3. temperaturethe reaction mixture was cooled
  4. custom1,4-dioxane was evaporated under reduced pressure
  5. customto afford initial product
  6. customThe initial product was purified by column chromatography

Sources & evidence

ORD record
ord-a758d8b335e84e1c99bd1ba6f79cb5ff
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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