Lithium Hydroxide → HCID 56928763, compound

HRID 1772146Notes

Reaction equation

HRID 1772146 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:18]=3)[C:13]2=[O:25])=[CH:10][CH:9]=[CH:8][C:7]=1[C:26]1[CH:31]=[C:30]([NH2:32])[C:29](=[O:33])[N:28]([CH3:34])[CH:27]=1)(=O)C.Cl[C:36]1[N:37]=[N:38][C:39]([N:42]2[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]2)=[CH:40][CH:41]=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.[OH-].[Li+]>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(O)C.C1COCC1.O1CCOCC1>[C:21]([C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:25])[N:12]([C:11]1[CH:10]=[CH:9][CH:8]=[C:7]([C:26]3[CH:31]=[C:30]([NH:32][C:36]4[N:37]=[N:38][C:39]([N:42]5[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]5)=[CH:40][CH:41]=4)[C:29](=[O:33])[N:28]([CH3:34])[CH:27]=3)[C:6]=1[CH2:5][OH:4])[CH2:20]2)([CH3:23])([CH3:24])[CH3:22]

Participants

11

Reactant 5

HCID 3939Lithium HydroxideHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 70988653-Chloro-6-(4-methylpiperazin-1-yl)pyridazineHCID 86699871HCID 86699871, compound

Product 1

HCID 56928763HCID 56928763, compound

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

A 100-mL three-neck round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and reflux condenser was charged with 122d (550 mg, 1.19 mmol), 122e (255 mg, 1.19 mmol), cesium carbonate (860 mg, 2.64 mmol) and 1,4-dioxane (20 mL). After bubbling nitrogen through the resulting mixture for 20 minutes, Xantphos (59.0 mg, 0.102 mmol) and tris(dibenzylideneacetone)dipalladium(0) (55.0 mg, 0.06 mmol) were added, and the reaction mixture was heated at reflux for 5 h. After this time, the reaction was cooled to room temperature, filtered and concentrated under reduced pressure to afford a brown residue. Another 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with residue obtained above, THF (10 mL), ethanol (10 mL), water (10 mL) and lithium hydroxide (115 mg, 4.80 mmol). The mixture was stirred at 50° C. for 2 h. After this time, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford a 23% (165 mg) yield of 122 as a white solid: mp 171-172° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.66 (d, 1H, J=2.0 Hz), 8.57 (s, 1H), 7.72 (d, 1H, J=8.5 Hz), 7.71 (s, 1H), 7.61 (d, 1H, J=8.0, 1.5 Hz), 7.54 (d, 1H, J=9.5 Hz), 7.50 (t, 1H, J=8.0 Hz), 7.45 (dd, 1H, J=8.0, 1.5 Hz), 7.38-7.36 (m, 2H), 7.30 (d, 1H, J=9.5 Hz), 4.94 (s, 2H), 4.84 (t, 1H, J=5.0 Hz), 4.34 (d, 2H, J=5.0 Hz), 3.60 (s, 3H), 3.41 (t, 4H, J=5.0 Hz), 2.39 (t, 4H, J=5.0 Hz), 2.20 (s, 3H), 1.36 (s, 9H); MS (ESI+) m/z 594.3 (M+H).

Workup

  1. customA 100-mL three-neck round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet
  2. temperaturereflux condenser
  3. customAfter bubbling nitrogen through the resulting mixture for 20 minutes
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 5 h
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto afford a brown residue
  9. customAnother 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  10. temperaturereflux condenser
  11. additionwas charged with residue
  12. customobtained above
  13. concentrationAfter this time, the reaction mixture was concentrated under reduced pressure
  14. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-495ca730d96a42239aa05f8af0011b4f
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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