Triethylamine → (+)-8-Chloro-6,11-dihydro-11-[4-(4-pyridinylmethyl)-1-piperazinyl]-5h-benzo[5,6]cyclohepta-[1,2-b]pyridine

HRID 21415Notes

Reaction equation

HRID 21415 reaction equation
[CH:1]1[C:6]([CH2:7]O)=[CH:5][CH:4]=[N+:3]([O-])[CH:2]=1.C(Br)(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:34][C:35]1[CH:36]=[CH:37][C:38]2[CH:48]([N:49]3[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]3)[C:43]3=[N:44][CH:45]=[CH:46][CH:47]=[C:42]3[CH2:41][CH2:40][C:39]=2[CH:55]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:34][C:35]1[CH:36]=[CH:37][C:38]2[CH:48]([N:49]3[CH2:50][CH2:51][N:52]([CH2:7][C:6]4[CH:5]=[CH:4][N:3]=[CH:2][CH:1]=4)[CH2:53][CH2:54]3)[C:43]3=[N:44][CH:45]=[CH:46][CH:47]=[C:42]3[CH2:41][CH2:40][C:39]=2[CH:55]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 896664-Pyridylmethanol N-oxideHCID 5255691HCID 5255691, compound

Product 1

HCID 19933864(+)-8-Chloro-6,11-dihydro-11-[4-(4-pyridinylmethyl)-1-piperazinyl]-5h-benzo[5,6]cyclohepta-[1,2-b]pyridineYield 75.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 213 mg (1.70 mmol) of 4-pyridylcarbinol N-oxide and 563 mg (1.70 mmol) of carbon tetrabromide in 14 mL of dry methylene chloride at room temperature and under an argon atmosphere was added in one portion 446 mg (1.70 mmol) of triphenylphosphine. After 45 minutes, 313 mg (0.997 mmol) of (+)-8-chloro-6,11-dihydro-11-(4-piperazinyl)-5H-benzo[5,6]cyclohepta-[1,2-b]pyridine was added followed by 237 mL (1.78 mmol) of triethylamine. The reaction mixture was then allowed to stir at room temperature overnight, after which it was taken up in methylene chloride and washed once with 0.5M aqueous sodium bicarbonate and then brine. The organic portion was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified via flash chromatography (5% methanol saturated with ammonia in methylene chloride) to provide 305 mg of (+)-8-chloro-6,11-dihydro-11-[4-(4-pyridinylmethyl)-1-piperazinyl]-5h-benzo[5,6]cyclohepta-[1,2-b]pyridine, N-oxide as a glass: MS (CI) m/z 421 (M+ +1);

Workup

  1. washwashed once with 0.5M aqueous sodium bicarbonate
  2. dry with materialThe organic portion was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via flash chromatography (5% methanol saturated with ammonia in methylene chloride)

Sources & evidence

ORD record
ord-3dacc96711b8470ba5079de702b983da
Source dataset
uspto-grants-1995_06
Patent number
US05422351

Reaction notes

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