Triethylamine → HCID 69606756, compound

HRID 859919Notes

Reaction equation

HRID 859919 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[N:7][CH:8]=1)#[CH:2].Br[C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][N:24]=1.C(N(CC)CC)C>CC(N(C)C)=O>[F:30][C:29]([F:32])([F:31])[C:26]1[CH:27]=[CH:28][C:23]([C:2]#[C:1][C:3]2[CH:4]=[CH:5][C:6]([N:9]3[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]3)=[N:7][CH:8]=2)=[N:24][CH:25]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27364342-Bromo-5-(trifluoromethyl)pyridineHCID 86594844HCID 86594844, compound

Product 1

HCID 69606756HCID 69606756, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred solution of tert-butyl 4-(5-ethynylpyridin-2-yl)piperazine-1-carboxylate (509 mg, 1.77 mmol), 2-Bromo-5-trifluoromethylpyridine (400 mg, 1.77 mmol), triethylamine (0.74 mL, 5.31 mmol), and cuprous iodide (135 mg, 0.71 mmol) in DMA (20 mL) at 25° C. was added tetrakistriphenylphosphine palladium (0) (102 mg, 5 mol %). The reaction was then stirred for 1 hour. Volatiles were removed in vacuo, and the residue was azeotroped with toluene (2×10 mL). The residue was then dissolved in CH2Cl2 (10 mL) and washed with water (10 mL). The layers were then separated and the aqueous phase extracted with CH2Cl2 (2×100 mL). The combined organic extracts were then dried, (MgSO4), filtered and concentrated in vacuo. The residue was then purified by flash chromatography (silica gel, 25% EtOAc in hexanes) to give tert-butyl 4-(5-{[5-(trifluoromethyl)pyridin-2-yl]ethynyl}pyridin-2-yl)piperazine-1-carboxylate as a yellow solid (729 mg, 1.68 mmol, 95%).

Workup

  1. customVolatiles were removed in vacuo
  2. customthe residue was azeotroped with toluene (2×10 mL)
  3. dissolutionThe residue was then dissolved in CH2Cl2 (10 mL)
  4. washwashed with water (10 mL)
  5. customThe layers were then separated
  6. extractionthe aqueous phase extracted with CH2Cl2 (2×100 mL)
  7. dry with materialThe combined organic extracts were then dried, (MgSO4),
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was then purified by flash chromatography (silica gel, 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-377b485a81e940e992fb551998def9b8
Source dataset
uspto-grants-2006_12
Patent number
US07153857B2

Reaction notes

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