Hydrochloric Acid → HCID 69086111, compound

HRID 1023419Notes

Reaction equation

HRID 1023419 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[N:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[N:10]=[CH:11][CH:12]=2)[CH:5]=[CH:4][N:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[Li+].C[Si]([N-:50][Si](C)(C)C)(C)C.Cl>C1COCC1.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>[F:19][C:16]1[CH:17]=[CH:18][C:13]([N:9]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH2:50])[CH:7]=3)=[CH:12][CH:11]=[N:10]2)=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 18676092HCID 18676092, compound

Product 1

HCID 69086111HCID 69086111, compoundYield 55.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
65 °C

Procedure

A 10 mL vial is charged with 2-Chloro-4-[2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-pyridine (160 mg, 0.59 mmol), Tris(dibenzylideneacetone)dipalladium (54 mg, 0.058 mmol) and 2-(dicyclohexylphosphino)biphenyl (53.3 mg, 0.15 mmol) in dry THF (3 mL) and Argon is bubbled through the mixture for 5 min. Additional THF (1 mL) and LiHMDS (1M in toluene, 1.14 mL, 1.5 mmol) are added and the reaction mixture is heated at 65° C. for 14 hours. Then 5 mL of 3.0 M HCl solution is added and the mixture is stirred for 10 min. Additional water (10 mL) is added and the mixture is extracted with EtOAc (2×10 mL). The aqueous layer is separated and its pH is adjusted to 10 by adding saturated Na2CO3 aquaous solution. The mixture is then extracted with EtOAc three times and the organic layers are combined, washed with brine and dried over anhdrous Na2SO4. Removal of solvent gives the desired product (83 mg).

Workup

  1. customis bubbled through the mixture for 5 min
  2. extractionthe mixture is extracted with EtOAc (2×10 mL)
  3. customThe aqueous layer is separated
  4. additionby adding saturated Na2CO3 aquaous solution
  5. extractionThe mixture is then extracted with EtOAc three times
  6. washwashed with brine
  7. dry with materialdried over anhdrous Na2SO4
  8. customRemoval of solvent

Sources & evidence

ORD record
ord-e9e5fe1ee0c44ff79135d827c26df775
Source dataset
uspto-grants-2014_05
Patent number
US08722709B2

Reaction notes

Loading…