7-nitro-1H-indole-2-carboxylic acid → HCID 69681052, compound

HRID 392769Notes

Reaction equation

HRID 392769 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([OH:15])=O)=[CH:9]2)([O-:3])=[O:2].Cl.CN(C)CCCN=C=NCC.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>ClCCl>[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][N:38]([C:13]([C:10]2[NH:11][C:12]3[C:8]([CH:9]=2)=[CH:7][CH:6]=[CH:5][C:4]=3[N+:1]([O-:3])=[O:2])=[O:15])[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

5

Reactant 3

HCID 814097-nitro-1H-indole-2-carboxylic acidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 69681052HCID 69681052, compoundYield 66.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 7-nitroindole-2-carboxylic acid (4.38 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.89 g) in dichloromethane (50 mL) was treated with piperazine-1-carboxylic acid tert-butyl ester (1.63 g) and stirred at ambient temperature for 16 h. The reaction mixture was poured into in dichloromethane (20 mL), washed with water, saturated sodium hydrogencarbonate solution and then brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified via silica gel chromatography (0-5% methanol/dichloromethane) to give 4-(7-Nitro-1H-indole-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester (2.17 g). This material (1.69 g) was dissolved in CH3OH (50 mL). At room temperature, ammonium formate (2.85 g) was added, followed by 10% palladium on carbon (0.47 g). The reaction mixture was heated to reflux for forty min, cooled and filtered through celite pad. The filtrate was concentrated and the residue was purified via silica gel chromatography (0-10% methanol/dichloromethane) to give 4-(7-Amino-1H-indole-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester (1.34 g). This material (1.3 g) was treated with 20% trifluoroacetic acid/dichloromethane (50 mL) and stirred at ambient temperature for 1 h. The solvent was removed under reduced pressure to afford (7-Amino-1H-indol-2-yl)-piperazin-1-yl-methanone trifluoroacetate salt. This intermediate was dissolved in dichloromethane (100 mL), washed with saturated sodium hydrogencarbonate solution and then brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified via silica gel chromatography (0-10% 2M ammonia in methanol/dichloromethane) to give the title compound (0.824 g). 1H NMR (400 MHz, CDCl3/CD3OD): δ 7.09 (d, J=7.83 Hz, 1H), 6.95 (t, J=7.63 Hz, 1H), 6.72 (s, 1H), 6.60 (d, J=7.63 Hz, 1H), 4.20 (br s, 4H), 3.88 (br s, 4H), 2.94 (t, J=5.09 Hz, 3H). MS (electrospray): exact mass calculated for C13H16N4O, 244.13; m/z found, 245.1 [M+H]+.

Workup

  1. washwashed with water, saturated sodium hydrogencarbonate solution
  2. dry with materialbrine, dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified via silica gel chromatography (0-5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-f883f5bf167f46378fe7b948c9f066d9
Source dataset
uspto-grants-2004_10
Patent number
US06803362B2

Reaction notes

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