1'-Methyl-6,7-dihydro-2H,5H-spiro[furo[2,3-f]indole-3,4'-piperidine] → 1'-Methyl-5-(2'-methyl-4'-pyrazinylbiphenyl-4-carbonyl)-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine]

HRID 1741121Notes

Reaction equation

HRID 1741121 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:18]3[C:10](=[CH:11][C:12]4[CH2:13][CH2:14][NH:15][C:16]=4[CH:17]=3)[O:9][CH2:8]2)[CH2:4][CH2:3]1.C[Al](C)C.[CH3:23][C:24]1[CH:29]=[C:28]([C:30]2[CH:35]=[N:34][CH:33]=[CH:32][N:31]=2)[CH:27]=[CH:26][C:25]=1[C:36]1[CH:41]=[CH:40][C:39]([C:42](OC)=[O:43])=[CH:38][CH:37]=1>C1(C)C=CC=CC=1.ClCCl>[CH3:1][N:2]1[CH2:3][CH2:4][C:5]2([C:18]3[C:10](=[CH:11][C:12]4[CH2:13][CH2:14][N:15]([C:42]([C:39]5[CH:38]=[CH:37][C:36]([C:25]6[CH:26]=[CH:27][C:28]([C:30]7[CH:35]=[N:34][CH:33]=[CH:32][N:31]=7)=[CH:29][C:24]=6[CH3:23])=[CH:41][CH:40]=5)=[O:43])[C:16]=4[CH:17]=3)[O:9][CH2:8]2)[CH2:6][CH2:7]1

Participants

6

Reactant 3

HCID 106579521'-Methyl-6,7-dihydro-2H,5H-spiro[furo[2,3-f]indole-3,4'-piperidine]HCID 16682925TrimethylaluminumHCID 21833780HCID 21833780, compound

Product 1

HCID 218337401'-Methyl-5-(2'-methyl-4'-pyrazinylbiphenyl-4-carbonyl)-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine]Yield 44%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

1'-Methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (0.098 g, 0.403 mmol) (D8) was dissolved in toluene (5 ml) and was treated with trimethylaluminium (2.0 M in hexane) (0.810 ml, 1.612 mmol) with stirring under argon. After 0.25 h, a solution of methyl 2'-methyl-4'-pyrazinylbiphenyl-4-carboxylate (D86, 0.136 g, 0.447 mmol) in toluene (5 ml) was added. The reaction mixture was then heated to 80° C. After 2 h, the reaction mixture was allowed to cool and was stirred at room temperature. The reaction mixture was then poured onto a slurry of silica gel (9385~20 ml) in dichloromethane (30 ml). After effervescence had ceased, the slurry was filtered and the filter pad was washed with 20% MeOH/CH2Cl2 (~200 ml). The filtrate was then evaporated under reduced pressure to give a brown oil, which was purified by silica-gel chromatography (9385, 10% MeOH/CH2Cl2 as eluant) to give the title compound as a cream solid (0.091 g, 44%).

Workup

  1. waitAfter 2 h
  2. temperatureto cool
  3. stirringwas stirred at room temperature
  4. filtrationthe slurry was filtered
  5. washthe filter pad was washed with 20% MeOH/CH2Cl2 (~200 ml)
  6. customThe filtrate was then evaporated under reduced pressure
  7. customto give a brown oil, which
  8. customwas purified by silica-gel chromatography (9385, 10% MeOH/CH2Cl2 as eluant)

Sources & evidence

ORD record
ord-f6f1866f89ea47cd8dcc23e2ddf1d4a4
Source dataset
uspto-grants-1999_10
Patent number
US05972951

Reaction notes

Loading…