Ethyl orthoformate → 2,3,5,6,7,8-Hexahydro-1'-methyl-5-(2'-methyl-4'-(1,3,4-oxadiazol-2-yl)biphenyl-4-carbonyl)spiro[furo[2,3-g]quinoline-3,4'-piperidine]

HRID 1741120Notes

Reaction equation

HRID 1741120 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:19]3[C:10](=[CH:11][C:12]4[CH2:13][CH2:14][CH2:15][N:16]([C:20]([C:22]5[CH:27]=[CH:26][C:25]([C:28]6[CH:33]=[CH:32][C:31]([C:34]([NH:36][NH2:37])=[O:35])=[CH:30][C:29]=6[CH3:38])=[CH:24][CH:23]=5)=[O:21])[C:17]=4[CH:18]=3)[O:9][CH2:8]2)[CH2:4][CH2:3]1.[CH2:39](OC(OCC)OCC)C>>[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:19]3[C:10](=[CH:11][C:12]4[CH2:13][CH2:14][CH2:15][N:16]([C:20]([C:22]5[CH:23]=[CH:24][C:25]([C:28]6[CH:33]=[CH:32][C:31]([C:34]7[O:35][CH:39]=[N:37][N:36]=7)=[CH:30][C:29]=6[CH3:38])=[CH:26][CH:27]=5)=[O:21])[C:17]=4[CH:18]=3)[O:9][CH2:8]2)[CH2:4][CH2:3]1

Participants

3

Reactant 2

HCID 31214Ethyl orthoformateHCID 218337492,3,5,6,7,8-Hexahydro-1'-methyl-5-(4'-hydrazinocarbonyl-2'-methylbiphenyl-4-carbonyl)spiro[furo[2,3-g]quinoline-3,4'-piperidine]

Product 1

HCID 218338282,3,5,6,7,8-Hexahydro-1'-methyl-5-(2'-methyl-4'-(1,3,4-oxadiazol-2-yl)biphenyl-4-carbonyl)spiro[furo[2,3-g]quinoline-3,4'-piperidine]Yield 58%

Procedure

A suspension of 2,3,5,6,7,8-hexahydro-1'-methyl-5-(4'-hydrazinocarbonyl-2'-methylbiphenyl-4-carbonyl)spiro[furo[2,3-g]quinoline-3,4'-piperidine] (E49) (794 mg) in triethylorthoformate (25 ml) was heated at reflux overnight. The mixture was concentrated in vacuo and the residue refluxed overnight in xylene (40 ml) to complete cyclisation. The xylene was evaporated under reduced pressure and the residue purified by chromatography on silica gel, eluting with chloroform and methanol, to afford the title compound (470 mg, 58%). The hydrochloride salt precipitated from acetone as a white solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. concentrationThe mixture was concentrated in vacuo
  4. temperaturethe residue refluxed overnight in xylene (40 ml)
  5. customThe xylene was evaporated under reduced pressure
  6. customthe residue purified by chromatography on silica gel
  7. washeluting with chloroform and methanol

Sources & evidence

ORD record
ord-a4e1496de43940cba8a19fa4512d1fda
Source dataset
uspto-grants-1999_10
Patent number
US05972951

Reaction notes

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