1,1'-Carbonyldiimidazole → Selexipag

HRID 1271310Notes

Reaction equation

HRID 1271310 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][S:45]([NH2:48])(=[O:47])=[O:46].CCCCCCC=CCCC>O1CCCC1.O>[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:48][S:45]([CH3:44])(=[O:47])=[O:46])=[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:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 136496Undec-4-eneHCID 99318912-(4-((5,6-Diphenyl-2-pyrazinyl)(1-methylethyl)amino)butoxy)acetic acid

Product 1

HCID 9913767SelexipagYield 76.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under an argon atmosphere, to a solution of 300 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, 128 mg of 1,1′-carbonyl diimidazole 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, 69 mg of methanesulfonamide was added. After stirring for 10 minutes, 0.11 ml of 1,8-diazabicyclo[5.4.0.]-7-undecene was added dropwise. After stirring at room temperature overnight, the reaction solution was diluted with water and then extracted with diethyl ether. The extract was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography to obtain 272 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. extractionextracted with diethyl ether
  7. dry with materialThe extract was dried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-932f4e453e394590a84664622dbffbec
Source dataset
uspto-grants-2007_04
Patent number
US07205302B2

Reaction notes

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