Triethylamine → HCID 68776249, compound

HRID 2262961Notes

Reaction equation

HRID 2262961 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](C(O)=O)=[CH:3]1.C([N:16]([CH2:19]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:28])C=CC=CC=1.[C:38]1([C:44]2[N:48]=[C:47]([N:49]3[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]3)[S:46][N:45]=2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1(C)C=CC=CC=1.O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([NH:16][C:19]([N:52]2[CH2:53][CH2:54][N:49]([C:47]3[S:46][N:45]=[C:44]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)[N:48]=3)[CH2:50][CH2:51]2)=[O:28])=[CH:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 8540401-Methylindole-3-carboxylic acidHCID 27777601-(3-Phenyl-(1,2,4)thiadiazol-5-yl)-piperazine

Product 1

HCID 68776249HCID 68776249, compoundYield 17.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 1-methylindole-3-carboxylic acid (175 mg, 1.00 mmol) and triethylamine (0.293 ml, 2.10 mmol) in toluene (10 ml) was added diphenylphosphoryl azide (0.226 ml, 1.05 mmol) at room temperature, and the mixture was stirred at room temperature for 30 minutes, followed by elevating the temperature to 90° C. and stirring for 1 hour and half. The resulting mixture was cooled to room temperature, 1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine (172 mg, 0.700 mmol) was added thereto, and the mixture was stirred at room temperature for 2.5 hours. Water was poured to the reaction mixture, and the resulting solution was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by high performance liquid chromatography (YMC HPLC Column eluted with 10% to 100% Liquid A; Liquid A: a 0.1% solution of trifluoroacetic acid in acetonitrile; Liquid B: an aqueous 0.1% trifluoroacetic acid solution) and recrystallized from a mixed solvent of hexane and tetrahydrofuran to give 52.4 mg (17.9%) of the desired product as a solid.

Workup

  1. customto 90° C.
  2. stirringstirring for 1 hour
  3. temperatureThe resulting mixture was cooled to room temperature
  4. stirringthe mixture was stirred at room temperature for 2.5 hours
  5. extractionthe resulting solution was extracted with ethyl acetate
  6. washThe extract was washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue was purified by high performance liquid chromatography (YMC HPLC Column
  10. washeluted with 10% to 100% Liquid A
  11. customLiquid B: an aqueous 0.1% trifluoroacetic acid solution) and recrystallized from a mixed solvent of hexane and tetrahydrofuran

Sources & evidence

ORD record
ord-6850debdde2b4692bfef44a4067c949a
Source dataset
uspto-grants-2010_12
Patent number
US07851473B2

Reaction notes

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