Indole → 5,6,7,8,9,10-Hexahydro-7,10-iminocyclohept[b]indole

HRID 1655269Notes

Reaction equation

HRID 1655269 reaction equation
[C:1]1([NH:7]N)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[C:10]1[CH:15]=[CH:14][C:13]([NH:16]N)=[CH:12][CH:11]=1.[CH2:18]1[CH:25]2[NH:26][CH:20]([CH2:21][C:22]([CH2:24]2)=O)[CH2:19]1.C[N:28]1[C@@H:33]2[CH2:34][C:35]([CH2:37][C@H:29]1[CH2:30][CH2:31][CH2:32]2)=O.N1C2C(=CC=CC=2)C=C1>>[NH:26]1[CH:25]2[C:24]3[C:6]4[C:1](=[CH:2][CH:3]=[CH:4][CH:5]=4)[NH:7][C:22]=3[CH2:21][CH:20]1[CH2:19][CH2:18]2.[NH:28]1[CH:29]2[C:30]3[C:14]4[C:13](=[CH:12][CH:11]=[CH:10][CH:15]=4)[NH:16][C:31]=3[CH2:32][CH:33]1[CH2:34][CH2:35][CH2:37]2

Participants

7

Reactant 5

HCID 798IndoleHCID 7516PhenylhydrazineHCID 69982(4-Fluorophenyl)hydrazineHCID 4344538-Azabicyclo(3.2.1)octan-3-oneHCID 6602484552-70-5

Product 2

HCID 151494265,6,7,8,9,10-Hexahydro-7,10-iminocyclohept[b]indoleHCID 15646125HCID 15646125, compound

Procedure

Accordingly, phenylhydrazine or 4-fluorophenylhydrazine is condensed with nortropinone or pseudo-pelletierine (9-azabicyclo-[3.2.1]nonan-3-one) under conditions of the Fischer indole synthesis to afford 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole or 6,7,8,9,10,11-hexahydro-7,11-imino-5H-cyclooct[b]indole or the corresponding-2-fluoro derivatives. Alkylation of the basic nitrogen in these compounds with the appropriately substituted alkyl halide or tosylate in dimethylformamide affords the compounds of Formula I wherein R1 is hydrogen. Alternatively, compounds of Formula I may be obtained by acylation of the hexahydro-7,10-iminocyclohept[b]indole or hexahydro-7,11-imino-5H-cyclooct[b]indole followed by reduction of the resulting amide with, for example, lithium aluminum hydride. Compounds of Formula I in which R1 is other than hydrogen or phenyl are prepared by abstraction of the a proton from the indole nitrogen, for example with sodium hydride in dimethylformamide, followed by reaction of the resulting anion with the required alkyl or aralkyl halide. Compounds of Formula I in which R1 is phenyl are prepared by alkylation or acylation/reduction of 5-phenyl-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept-[b]indole (J. G. Berger and P. Tahbaz, U.S. Pat. No. 4,360,673, Nov. 23, 1982) or 5-phenyl-6,7,8,9,10,11-hexahydro-7,11-imino-5H-cyclooct[b]indole as outlined above.

Sources & evidence

ORD record
ord-b54193ad83a24fdb95130fb1ce65bb2b
Source dataset
uspto-grants-1993_10
Patent number
US05250537

Reaction notes

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