Ammonium Chloride → HCID 69083700, compound

HRID 1023456Notes

Reaction equation

HRID 1023456 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]2[N:9]([CH3:20])[CH:10]=[N:11][C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[Li+].C[Si]([N-:51][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:19][C:16]1[CH:17]=[CH:18][C:13]([C:12]2[N:11]=[CH:10][N:9]([CH3:20])[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:51])[CH:7]=2)=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 86673610HCID 86673610, compound

Product 1

HCID 69083700HCID 69083700, compoundYield 4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Bromo-4-[5-(4-fluoro-phenyl)-3-methyl-3H-imidazol-4-yl]-pyridine (460 mg, 1.39 mmol), tris(dibenzylideneacetone)dipalladium(0) (254 mg, 0.28 mmol) and 2-(dicyclohexylphosphino)biphenyl (252 mg, 0.72 mmol) are mixed in dry THF (10 mL). Then Argon is bubbled through the solution for 5 min and 1.0 M LiHMDS (4.8 mL, 4.8 mmol) is added. Then the reaction mixture is heated at 65° C. for 16 hrs before the saturated NH4Cl aqueous solution (20 mL) is added along with water (25 mL). The mixture is extracted with EtOAc (3×50 mL) and the organic layers are combined and concentrated to give the crude product. Purification by silica flash column chromatography using MeOH in DCM (gradient from 0% to 10%) followed by Gilson preparative HPLC affords 15 mg of desired product.

Workup

  1. customThen Argon is bubbled through the solution for 5 min
  2. extractionThe mixture is extracted with EtOAc (3×50 mL)
  3. concentrationconcentrated
  4. customto give the crude product
  5. customPurification by silica flash column chromatography

Sources & evidence

ORD record
ord-68c5f494803a406c8e2f18080e1356f1
Source dataset
uspto-grants-2014_05
Patent number
US08722709B2

Reaction notes

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