Triphosgene → HCID 24853021, compound

HRID 551815Notes

Reaction equation

HRID 551815 reaction equation
[CH3:1][S:2]([C:5]1[CH:21]=[CH:20][C:8]([CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][CH2:12][CH2:11]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].ClC(Cl)(O[C:26](=[O:32])OC(Cl)(Cl)Cl)Cl.Cl.Cl.[NH:36]1[CH2:40][CH2:39][CH:38]([C:41]2[CH:42]=[N:43][NH:44][CH:45]=2)[CH2:37]1.C(=O)([O-])O.[Na+]>ClCCl.CN1CCOCC1.O>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]([C:26]([N:36]3[CH2:40][CH2:39][CH:38]([C:41]4[CH:42]=[N:43][NH:44][CH:45]=4)[CH2:37]3)=[O:32])[CH2:12][CH2:11]2)=[CH:20][CH:21]=1)(=[O:3])=[O:4]

Participants

8

Reactant 4

HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 671872291000688-81-2HCID 67190176HCID 67190176, compound

Product 1

HCID 24853021HCID 24853021, compoundYield 34.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 79724-MethylmorpholineSolvent

Procedure

0.3 g of 4-(4-(methanesulfonyl)benzyl)-3,4-dihydro-2H-quinoxaline is dissolved in 10 ml of dichloromethane and 0.1 ml of N-methylmorpholine. 0.118 g of triphosgene is added at 0° C. and then the reaction mixture is left stirring at ambient temperature for four hours. 0.208 g of 4-(pyrrolidin-3-yl)-1H-pyrazole dihydrochloride is subsequently added and the reaction mixture is stirred for eighteen hours. A saturated solution of sodium hydrogencarbonate in water and dichloromethane are added. The aqueous phase is extracted twice with dichloromethane. The organic phases are combined, washed with water and with a saturated aqueous sodium chloride solution and dried over magnesium sulfate and then the solvent is evaporated under reduced pressure. The residue is chromatographed on silica gel, a first time with a gradient of dichloromethane/methanol 1/0 to 85/5 mixture and then a second time with a gradient of dichloromethane/ethyl acetate/methanol 1/0/0 to 70/25/5 mixture. 0.064 g of [4-(4-(methanesulfonyl)benzyl)-3,4-dihydro-2H-quinoxalin-1-yl][3-(1H-pyrazol-4-yl)pyrrolidin-1-yl]methanone is obtained.

Workup

  1. waitthe reaction mixture is left
  2. stirringthe reaction mixture is stirred for eighteen hours
  3. extractionThe aqueous phase is extracted twice with dichloromethane
  4. washwashed with water and with a saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. customthe solvent is evaporated under reduced pressure
  7. customThe residue is chromatographed on silica gel

Sources & evidence

ORD record
ord-69b2f4177485470f923cd30c240587f0
Source dataset
uspto-grants-2011_05
Patent number
US07947834B2

Reaction notes

Loading…