Cesium carbonate → HCID 89813717, compound

HRID 525356Notes

Reaction equation

HRID 525356 reaction equation
[CH2:1]([C:3]1([CH2:15][CH3:16])[O:7][C:6](=[O:8])[NH:5][C@H:4]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:2].I[C:18]1[CH:36]=[CH:35][C:21]([C:22]([NH:24][C:25]2[CH:26]=[CH:27][CH:28]=[C:29]3[C:34]=2[N:33]=[CH:32][CH:31]=[CH:30]3)=[O:23])=[CH:20][CH:19]=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>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.O1CCOCC1>[CH2:15]([C:3]1([CH2:1][CH3:2])[O:7][C:6](=[O:8])[N:5]([C:18]2[CH:36]=[CH:35][C:21]([C:22]([NH:24][C:25]3[CH:26]=[CH:27][CH:28]=[C:29]4[C:34]=3[N:33]=[CH:32][CH:31]=[CH:30]4)=[O:23])=[CH:20][CH:19]=2)[C@H:4]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:16]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 41661718HCID 41661718, compoundHCID 89814220HCID 89814220, compound

Product 1

HCID 89813717HCID 89813717, compoundYield 7.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 25 mL round bottom flask were added (S)-5,5-diethyl-4-phenyloxazolidin-2-one (0.3 g, 1.36 mmol), 4-iodo-N-(quinolin-8-yl)benzamide (0.560 g, 1.5 mmol), Cs2CO3 (0.972 g, 3.0 mmol), X-Phos (35 mg, 0.068 mmol), Pd2(dba)3 (62 mg, 0.068 mmol) and 1,4-dioxane (2 mL). The mixture was purged with N2 gas for 15 minutes. The reaction mixture was then heated at 90° C. for 6 hours. After completion of reaction (monitored by TLC, TLC eluent: 30% EtOAc in hexane), the reaction mixture was cooled to ambient temperature and treated with water (5 mL) and the mixture extracted with EtOAc (5 mL). The aqueous layer was back extracted with EtOAc (5 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated. The crude material was purified with HPLC (column: AG/AD/C18-027, ramping ACN in H2O, 40-50% B, 0-2 minutes, 50-90% B, 2-10 minutes, flow rate 20 mL/min) to afford 50 mg of (S)-4-(5,5-diethyl-2-oxo-4-phenyloxazolidin-3-yl)-N-(quinolin-8-yl)benzamide as a brown solid. 1H NMR (300 MHz, CDCl3) δ: 10.67 (s, 1H), 8.96-8.80 (m, 2H), 8.20 (dd, J=8.3, 1.6 Hz, 1H), 7.99 (d, J=9 Hz, 2H), 7.68 (d, J=8.7 Hz, 2H), 7.62-7.56 (m, 2H), 7.57-7.47 (m, 1H), 7.40-7.36 (m, 3H), 7.28-7.24 (m, 2H), 5.15 (s, 1H), 2.04-1.96 (m, 2H), 1.39-1.20 (m, 2H), 1.12 (t, J=7.5 Hz, 3H), 0.85 (t, J=7.4 Hz, 3H). m/z (ESI) 466.2 (M+H)+.

Workup

  1. customThe mixture was 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 to ambient temperature
  4. extractionthe mixture extracted with EtOAc (5 mL)
  5. extractionThe aqueous layer was back extracted with EtOAc (5 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customThe crude material was purified with HPLC (column: AG/AD/C18-027, ramping ACN in H2O, 40-50% B, 0-2 minutes, 50-90% B, 2-10 minutes, flow rate 20 mL/min)

Sources & evidence

ORD record
ord-9ba411976d534547b2d850f119b9cb9d
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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