P-Toluenesulfonamide → 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(p-toluenesulfonyl)acetamide

HRID 1271311Notes

Reaction equation

HRID 1271311 reaction equation
[C:1]1([C:7]2[N:8]=[CH:9][C:10]([N:19]([CH2:23][CH2:24][CH2:25][CH2:26][O:27][CH2:28][C:29](O)=[O:30])[CH:20]([CH3:22])[CH3:21])=[N:11][C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:44][C:45]1[CH:46]=[CH:47][C:48]([S:51]([NH2:54])(=[O:53])=[O:52])=[CH:49][CH:50]=1.CCCCCCC=CCCC>O1CCCC1>[C:1]1([C:7]2[N:8]=[CH:9][C:10]([N:19]([CH2:23][CH2:24][CH2:25][CH2:26][O:27][CH2:28][C:29]([NH:54][S:51]([C:48]3[CH:49]=[CH:50][C:45]([CH3:44])=[CH:46][CH:47]=3)(=[O:52])=[O:53])=[O:30])[CH:20]([CH3:22])[CH3:21])=[N:11][C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 6269P-ToluenesulfonamideHCID 682631,1'-CarbonyldiimidazoleHCID 136496Undec-4-eneHCID 99318912-(4-((5,6-Diphenyl-2-pyrazinyl)(1-methylethyl)amino)butoxy)acetic acid

Product 1

HCID 184526142-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(p-toluenesulfonyl)acetamideYield 67.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 500 mg of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid obtained in Example 42 in 5 ml of anhydrous tetrahydrofuran, 214 mg of 1,1′-carbonyldiimidazole was added and, after stirring at room temperature for 30 minutes, the mixture was heated at reflux for 30 minutes. After air-cooling to room temperature, 206 mg of p-toluenesulfonamide was added. After stirring for 10 minutes, 0.18 ml of 1,8-diazabicyclo[5.4.0.]undec-7-ene was added dropwise. After stirring at room temperature overnight, almost all of the solvent was evaporated under reduced pressure. The residue was combined with water and then neutralized with 1N hydrochloric acid. The reaction solution was extracted with ethyl acetate and dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 460 mg of the desired compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 30 minutes
  3. temperatureAfter air-cooling to room temperature
  4. stirringAfter stirring for 10 minutes
  5. stirringAfter stirring at room temperature overnight
  6. customalmost all of the solvent was evaporated under reduced pressure
  7. extractionThe reaction solution was extracted with ethyl acetate
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-764d08c3c6d24604b7b71cc441175785
Source dataset
uspto-grants-2007_04
Patent number
US07205302B2

Reaction notes

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