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

HRID 924606Notes

Reaction equation

HRID 924606 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.[Cl:18][C:19]1[CH:24]=[C:23]([CH3:25])[C:22]([CH:26]([C:30](N)=[O:31])[C:27](N)=[O:28])=[C:21]([CH3:33])[CH:20]=1>C1(C)C(C)=CC=CC=1.ClCCl>[Cl:18][C:19]1[CH:20]=[C:21]([CH3:33])[C:22]([CH:26]2[C:30](=[O:31])[N:7]3[CH2:6][CH2:5][N:4]([O:3][CH3:2])[CH2:10][CH2:9][N:8]3[C:27]2=[O:28])=[C:23]([CH3:25])[CH:24]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 711451642-(4-Chloro-2,6-dimethyl-phenyl)-malonamideHCID 867199135-Methoxy-[1,2,5]triazepane hydrochloride salt

Product 1

HCID 867199228-(4-Chloro-2,6-dimethyl-phenyl)-3-methoxy-tetrahydro-pyrazolo[1,2-a][1,2,5]triazepine-7,9-dione

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 7237O-XyleneSolvent

Conditions

Temperature
60 °C

Procedure

A degassed suspension of 5-methoxy-[1,2,5]triazepane hydrochloride salt (100 mg, 0.49 mmol) and triethylamine (0.33 ml, 207 mg, 2.05 mmol) in xylene (2.5 ml) was stirred under argon at 60° C. for 30 minutes in a microwave vial. After further addition of 2-(4-chloro-2,6-dimethyl-phenyl)-malonamide (120 mg, 0.50 mmol), the vial was capped and irradiated twice with microwaves at 180° C. for 10 minutes. The solid deposit on the vial wall was dissolved in dichloromethane, the solvent evaporated, the oily residue dissolved in 5N aqueous sodium hydroxide, the aqueous layer extracted with ethyl acetate (3×) 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. Yield: 10 mg of 8-(4-chloro-2,6-dimethyl-phenyl)-3-methoxy-tetrahydro-pyrazolo[1,2-a][1,2,5]triazepine-7,9-dione (compound P2.2) as a beige solid.

Workup

  1. customthe vial was capped
  2. customirradiated twice with microwaves at 180° C. for 10 minutes
  3. customthe solvent evaporated
  4. dissolutionthe oily residue dissolved in 5N aqueous sodium hydroxide
  5. extractionthe aqueous layer extracted with ethyl acetate (3×)
  6. temperaturewith cooling to pH 2-3 by addition of a 4N HCl solution
  7. extractionthe product thoroughly extracted with dichloromethane
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3679da13838943688e2610df4a875fa2
Source dataset
uspto-grants-2016_03
Patent number
US09282743B2

Reaction notes

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