Hydrochloric Acid → HCID 58303636, compound

HRID 876452Notes

Reaction equation

HRID 876452 reaction equation
[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23](Cl)[CH:22]=4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[Li+].C[Si]([N-:67][Si](C)(C)C)(C)C.Cl>C1COCC1.O.ClCCl.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]>[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([NH2:67])[CH:22]=4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86654363HCID 86654363, compound

Product 1

HCID 58303636HCID 58303636, compoundYield 27.1%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-8-(2-chloropyridin-4-yloxy)quinoline (0.105 g, 0.281 mmol) in 71 mL THF (degassed with nitrogen 30 minutes prior to use) was added sequentially XPHOS (0.0107 g, 0.0225 mmol), Pd2 dba3 (0.0103 g, 0.0112 mmol), and 1M LHMDS in THF (0.590 mL, 0.590 mmol) by syringe. The reaction mixture was heated to reflux and stirred for 3 hours. The reaction mixture was cooled to 0° C. and 1M aqueous HCl (1.40 mL, 1.40 mmol) was added, causing milky solids to form. The reaction mixture was stirred 30 minutes, then diluted with water and dichloromethane, and the aqueous layer was washed with dichloromethane. The aqueous layer was basified with 1M NaOH (pH>10), and the milky mixture was extracted with chloroform. The combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified by preparative TLC (9:1 chloroform:6% NH4OH in methanol) to give the title compound (0.027 g, 0.0762 mmol, 27.1% yield) as a yellow/orange powder. MS APCI (+) m/z 355 (M+1) detected.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. customto form
  4. stirringThe reaction mixture was stirred 30 minutes
  5. washthe aqueous layer was washed with dichloromethane
  6. extractionthe milky mixture was extracted with chloroform
  7. dry with materialThe combined extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude was purified by preparative TLC (9:1 chloroform:6% NH4OH in methanol)

Sources & evidence

ORD record
ord-8803e06c7bd24de1881bb944e5b0a07f
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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