1-Hydroxybenzotriazole → 5-Amino-4-methyl-2-(1-methyl-piperidin-4-yl)-6-nitro-isoindole-1,3-dione

HRID 2361145Notes

Reaction equation

HRID 2361145 reaction equation
CO[C:3](=[O:18])[C:4]1[C:5](=[CH:9][C:10]([N+:15]([O-:17])=[O:16])=[C:11]([NH2:14])[C:12]=1[CH3:13])[C:6]([OH:8])=O.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.Cl.Cl.[NH2:43][CH:44]1[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]1>CCN(CC)CC>[NH2:14][C:11]1[C:12]([CH3:13])=[C:4]2[C:5](=[CH:9][C:10]=1[N+:15]([O-:17])=[O:16])[C:6](=[O:8])[N:43]([CH:44]1[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]1)[C:3]2=[O:18]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220025361-Methylpiperidin-4-amine dihydrochlorideHCID 597616804-Amino-2-(methoxycarbonyl)-3-methyl-5-nitrobenzoic acid

Product 1

HCID 597618595-Amino-4-methyl-2-(1-methyl-piperidin-4-yl)-6-nitro-isoindole-1,3-dioneYield 104.3%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a solution of 4-Amino-3-methyl-5-nitro-phthalic acid 2-methyl ester (1.3 g, 5.12 mmol), EDCI.HCl (1.07 g, 5.63 mmol) and HOBt (0.69 g, 5.12 mmol) was added Et3N (3.64 mL, 25.6 mL) and stirred at room temperature for 10 min. 4-Amino-1-methylpiperidine dihydrochloride (1.04 g, 5.63 mmol) was added and the resulting mixture was stirred at room temperature for 24 h. The reaction mixture was evaporated in vacuo, the residue was dissolved in CHCl3 (200 mL), washed with water (2×100 mL). The organic layer was filtered over Na2SO4 and concentrated in vacuo to afford 5-Amino-4-methyl-2-(1-methyl-piperidin-4-yl)-6-nitro-isoindole-1,3-dione (1.7 g, quant), which was used as such for further reaction.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 24 h
  2. customThe reaction mixture was evaporated in vacuo
  3. dissolutionthe residue was dissolved in CHCl3 (200 mL)
  4. washwashed with water (2×100 mL)
  5. filtrationThe organic layer was filtered over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bc56cdbc960c49dfa772d2e2d615f4af
Source dataset
uspto-grants-2014_04
Patent number
US08686005B2

Reaction notes

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