Cesium carbonate → HCID 178471736, compound

HRID 1778237Notes

Reaction equation

HRID 1778237 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[C:14]([OH:19])[CH:13]=[C:12]3Br)=[CH:4][CH:3]=1.[NH2:28][CH:29]1[CH2:34][CH2:33][N:32]([C:35](=[O:43])[CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:31][CH2:30]1.C([O-])([O-])=O.[Cs+].[Cs+].CC([O-])(C)C.[K+]>O.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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[C:14]([OH:19])[CH:13]=[C:12]3[NH:28][CH:29]2[CH2:34][CH2:33][N:32]([C:35](=[O:43])[CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:31][CH2:30]2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 23665647Potassium tert-butoxideHCID 64327902HCID 64327902, compoundHCID 178515443HCID 178515443, compound

Product 1

HCID 178471736HCID 178471736, compound

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 25-mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed 6-[bis(4-chlorophenyl)methyl]-4-bromoquinolin-2-ol (300 mg, 0.65 mmol, 1.00 equip, 99%), ethyl 4-(4-aminopiperidin-1-yl)-4-oxobutanoate (295.1 mg, 0.97 mmol, 1.50 equip), Pd2(dba)3 (60 mg, 0.06 mmol, 0.10 equip, 99%), dppf (126.7 mg, 0.23 mmol, 0.35 equip, 99%), Cs2CO3 (532.7 mg, 1.62 mmol, 2.50 equip, 99%), t-BuOK (146.4 mg, 1.29 mmol, 2.00 equip, 99%), and 1,4-dioxane (9 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The resulting solution was diluted with water (80 mL). The resulting solution was extracted with ethyl acetate (3×80 mL) and the organic layers combined. The resulting mixture was washed with water (1×80 mL) and brine (1×80 mL). The resulting mixture was dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The resulting residue was purified by Prep-HPLC with the following conditions: Column, Sunfire Prep C18 OBD 5 μm, 19×150 mm; mobile phase, Phase A: water (0.05% NH4HCO3), Phase B:CH3CN (20% CH3CN up to 80% in 8 min, up to 100% for 0.1 min, hold 100% in 1.9 min, down to 20% in 0.1 min, hold 20% in 1.9 min); Detector, UV 220 & 254 nm to yield ethyl 4-[4-([6-[bis(4-chlorophenyl)methyl]-2-hydroxyquinolin-4-yl]amino)piperidin-1-yl]-4-oxobutanoate as a white solid.

Workup

  1. customInto a 25-mL sealed tube
  2. custompurged
  3. temperaturemaintained with an inert atmosphere of nitrogen
  4. extractionThe resulting solution was extracted with ethyl acetate (3×80 mL)
  5. washThe resulting mixture was washed with water (1×80 mL) and brine (1×80 mL)
  6. dry with materialThe resulting mixture was dried over anhydrous sodium sulfate
  7. filtrationThe solids were filtered out
  8. concentrationThe resulting mixture was concentrated under vacuum
  9. customThe resulting residue was purified by Prep-HPLC with the following conditions
  10. waitmobile phase, Phase A: water (0.05% NH4HCO3), Phase B:CH3CN (20% CH3CN up to 80% in 8 min
  11. waitup to 100% for 0.1 min
  12. customin 1.9 min
  13. waitdown to 20% in 0.1 min
  14. customin 1.9 min

Sources & evidence

ORD record
ord-5df2c8f152f649da8042355b012a6b0a
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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