4-Nitro-1H-indole → 4-NITROGRAMINE

HRID 1884334Notes

Reaction equation

HRID 1884334 reaction equation
[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][NH:8]2)([O-:3])=[O:2].[CH2:13]=O.[CH3:15][NH:16][CH3:17]>>[CH3:15][N:16]([CH2:13][C:6]1[C:5]2[C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=[CH:10][C:9]=2[NH:8][CH:7]=1)[CH3:17]

Participants

3

Reactant 2

HCID 1457664-Nitro-1H-indoleHCID 23062016HCID 23062016, compound

Product 1

HCID 2514534-NITROGRAMINE

Procedure

Scheme M illustrates a general method of preparing compounds of the invention (for a synthesis of intermediate amine 8, see also J. Hester J. Org. Chem. 1967, 32, 4095). 4-Nitroindole and formaldehyde/dimethylamine were condensed to form 4-nitrogramine (2). Compound 2 underwent nucleophilic substitution with diethyl malonate to afford diester 3, which was then reduced to the amine 4 via hydrogenolysis over palladium-on-carbon. Indole 4 was cyclized thermally to lactam 5, and then underwent decarboxylation by treatment with potassium hydroxide followed by heating neat to give unsubstituted lactam 7. The lactam 7 was reduced with LAH to afford amine 8, which was acylated with acid chloride 9 (prepared by acylation of methyl 4-aminobenzoate with 2-biphenylcarbonyl chloride followed by sodium hydroxide-mediated saponification of the ester to the acid, and then thionyl chloride-mediated conversion to the acid chloride 9) to give the final product compound 10.

Workup

  1. customa general method of preparing compounds of the invention (
  2. customcondensed

Sources & evidence

ORD record
ord-42a06a5da9634e2895e396c0c98644b5
Source dataset
uspto-grants-2004_07
Patent number
US06765004B1

Reaction notes

Loading…