Triethylamine → 3-Methoxy-8-(2,4,6-trimethyl-phenyl)-tetrahydro-pyrazolo[1,2-a][1,2,5]triazepine-7,9-dione

HRID 924598Notes

Reaction equation

HRID 924598 reaction equation
Cl.[CH3:2][O:3][N:4]1[CH2:10][CH2:9][NH:8][NH:7][CH2:6][CH2:5]1.C(N(CC)CC)C.C([O:20][C:21](=O)[CH:22]([C:28]1[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=1[CH3:36])[C:23](OCC)=[O:24])C.[OH-].[Na+]>C1(C)C(C)=CC=CC=1>[CH3:2][O:3][N:4]1[CH2:10][CH2:9][N:8]2[C:21](=[O:20])[CH:22]([C:28]3[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=3[CH3:36])[C:23](=[O:24])[N:7]2[CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 17750528Diethyl (2,4,6-trimethylphenyl)propanedioateHCID 867199135-Methoxy-[1,2,5]triazepane hydrochloride salt

Product 1

HCID 867199153-Methoxy-8-(2,4,6-trimethyl-phenyl)-tetrahydro-pyrazolo[1,2-a][1,2,5]triazepine-7,9-dione

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
60 °C

Procedure

A degassed suspension of 5-methoxy-[1,2,5]triazepane hydrochloride salt (350 mg, 1.71 mmol) and triethylamine (1.0 ml, 726 mg, 7.17 mmol) in xylene (8 ml) was stirred under argon at 60° C. for one hour. After further addition of 2-(2,4,6-trimethyl-phenyl)-malonic acid diethyl ester (482 mg, 1.73 mmol), the reaction mixture was heated at 150° C. (oil bath temperature) for 18 hours. The cooled reaction mixture was poured on ice, the pH made alkaline by addition of 5N aqueous sodium hydroxide, the aqueous layer extracted twice with ethyl acetate and the combined organic layers discarded. The aqueous alkaline phase was acidified with cooling to pH 2-3 by addition of a 4N HCl solution and the product thoroughly extracted with dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The base-acidification workup protocol is repeated a second time. Yield: 24 mg of 3-methoxy-8-(2,4,6-trimethyl-phenyl)-tetrahydro-pyrazolo[1,2-a][1,2,5]triazepine-7,9-dione (compound P2.1) as a beige solid.

Workup

  1. temperaturethe reaction mixture was heated at 150° C. (oil bath temperature) for 18 hours
  2. customThe cooled reaction mixture
  3. additionwas poured on ice
  4. extractionthe aqueous layer extracted twice with ethyl acetate
  5. temperaturewith cooling to pH 2-3 by addition of a 4N HCl solution
  6. extractionthe product thoroughly extracted with dichloromethane
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-699bf99d308641058f14c2e9cead85db
Source dataset
uspto-grants-2016_03
Patent number
US09282743B2

Reaction notes

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