Sodium Chloride → HCID 66711401, compound

HRID 1262115Notes

Reaction equation

HRID 1262115 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][CH:17]=[C:18]3[C:23]=2[N:22]=[CH:21][C:20](I)=[CH:19]3)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].C(=[NH:86])(C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[Na+].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C1COCC1.Cl.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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][CH:17]=[C:18]3[C:23]=2[N:22]=[CH:21][C:20]([NH2:86])=[CH:19]3)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

12

Reactant 6

HCID 5234Sodium ChlorideHCID 136809Benzophenone imineHCID 516892Sodium BicarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 66711932HCID 66711932, compound

Product 1

HCID 66711401HCID 66711401, compoundYield 46.8%

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a 10-mL sealed tube was heated 4-(3-Iodoquinolin-8-yl)piperazine-1-carboxylic acid tert-butyl ester (520.0 mg, 1.184 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)-xanthene (137 mg, 0.2367 mmol), tris(dibenzylideneacetone)dipalladium(0) (108.4 mg, 0.1184 mmol), sodium tert-butoxide (341.3 mg, 3.551 mmol), and benzophenone imine (218 L, 1.30 mmol) in 13 mL toluene at 100° C. for 5 hours. The reaction was cooled and water and sodium chloride were added. The product was extracted with DCM, dried with sodium sulfate, filtered, and conc. in vacuo. Purification via silica gel chromatography eluting with 100:1 DCM:MeOH afforded the crude imine which was dissolved in 10 THF and treated with 10 drops of 12.1M aq. HCl at room temperature. Upon reaction completion, water and sat. NaHCO3 were added to the reaction whose contents were extracted with DCM. The combined extracts were dried with sodium sulfate, filtered, and conc. in vacuo. The crude material was purified via silica gel chromatography eluting with 50:1 DCM:MeOH to provide 4-(3-Aminoquinolin-8-yl)-piperazine-1-carboxylic acid tert-butyl ester as an off-white solid (182 mg, 44.5%). MP 168-173° C. LCMS (E/I+) 329.13 (M+H). 1H NMR (DMSO-d6)-8.37 (d, 1H, J=2.56 Hz), 7.23 (t, 1H, J=7.71 Hz), 7.18 (d, 1H, J=7.76 Hz), 7.08 (d, 1H, J=2.52 Hz), 6.74 (d, 1H, J=7.12 Hz), 5.58 (s, 2H), 3.59-3.51 (m, 4H), 3.25-3.19 (m, 4H), 1.43 (s, 9H).

Workup

  1. customIn a 10-mL sealed tube
  2. temperatureThe reaction was cooled
  3. extractionThe product was extracted with DCM
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. customPurification via silica gel chromatography
  7. washeluting with 100:1 DCM
  8. customMeOH afforded the crude imine which
  9. additionwere added to the reaction whose contents
  10. extractionwere extracted with DCM
  11. dry with materialThe combined extracts were dried with sodium sulfate
  12. filtrationfiltered
  13. customThe crude material was purified via silica gel chromatography
  14. washeluting with 50:1 DCM

Sources & evidence

ORD record
ord-2fea9b638ea04ec5abb1517fd49128f7
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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