Ammonium Chloride → HCID 69083646, compound

HRID 1023417Notes

Reaction equation

HRID 1023417 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[N:9]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[N:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=2)[CH:5]=[CH:4][N:3]=1.C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[Li+].C[Si]([N-:54][Si](C)(C)C)(C)C.[NH4+].[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:23][C:20]1[CH:21]=[CH:22][C:17]([N:9]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH2:54])[CH:7]=3)=[CH:12][C:11]([C:13]([F:16])([F:15])[F:14])=[N:10]2)=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium Hexamethyldisilazide2×HCID 27342162-(Dicyclohexylphosphino)biphenyl2×HCID 86673604HCID 86673604, compound

Product 1

HCID 69083646HCID 69083646, compoundYield 94.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
65 °C

Procedure

2-Chloro-4-[2-(4-fluoro-phenyl)-5-trifluoromethyl-2H-pyrazol-3-yl]-pyridine (120 mg, 0.35 mmol), Pd2(dba)3 (32 mg, 0.04 mmol) and biphenyl-2-yl-dicyclohexyl-phosphane (32 mg, 0.09 mmol) are mixed in a reaction vial and dry THF (2.0 mL) is added. Then Argon is bubbled through the solution for 5 min and 1.0 M LiHMDS (0.88 mL, 0.88 mmol) in THF is added. The reaction vial is sealed and heated at 65° C. for 16 hrs. More Pd2(dba)3 (32 mg, 0.04 mmol), biphenyl-2-yl-dicyclohexyl-phosphane (32 mg, 0.09 mmol) and 1.0 M LiHMDS (0.88 mL, 0.88 mmol) in THF are added and the reaction mixture is heated at 65° C. for another 5 hrs. Then saturated NH4Cl solution (20 mL) is added along with water (20 mL). The mixture is extracted with EtOAc (3×30 mL) and the organic layers are combined and concentrated to give the crude product. Purification by flash column chromatography using MeOH in DCM (gradient from 0% to 10%) affords 107 mg of product.

Workup

  1. additionis added
  2. customThen Argon is bubbled through the solution for 5 min
  3. customThe reaction
  4. customvial is sealed
  5. temperaturethe reaction mixture is heated at 65° C. for another 5 hrs
  6. extractionThe mixture is extracted with EtOAc (3×30 mL)
  7. concentrationconcentrated
  8. customto give the crude product
  9. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-1ca41e766e5d4a3bb679182ee91c2cf0
Source dataset
uspto-grants-2014_05
Patent number
US08722709B2

Reaction notes

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