Triphosgene → HCID 89771106, compound

HRID 711346Notes

Reaction equation

HRID 711346 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[CH2:13]([C:16]1([CH2:33][CH:34]=[CH2:35])[C:31](=[O:32])[N:19]2[CH2:20][CH2:21][NH:22][C@@H:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[CH3:30])[C@@H:18]2[CH2:17]1)[CH:14]=[CH2:15].[CH:36]([C:39]1[CH:40]=[C:41]([C@H:49]([NH:51][CH3:52])[CH3:50])[CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)([CH3:38])[CH3:37]>CCOC(C)=O.CN(C1C=CN=CC=1)C>[CH2:33]([C:16]1([CH2:13][CH:14]=[CH2:15])[C:31](=[O:32])[N:19]2[CH2:20][CH2:21][N:22]([C:5]([N:51]([C@@H:49]([C:41]3[CH:42]=[C:43]([C:45]([F:46])([F:47])[F:48])[CH:44]=[C:39]([CH:36]([CH3:38])[CH3:37])[CH:40]=3)[CH3:50])[CH3:52])=[O:11])[C@@H:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[CH3:30])[C@@H:18]2[CH2:17]1)[CH:34]=[CH2:35]

Participants

6

Reactant 3

HCID 94429TriphosgeneHCID 89771117HCID 89771117, compoundHCID 89771122HCID 89771122, compound

Product 1

HCID 89771106HCID 89771106, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent3×

Procedure

To a solution of triphosgene (72 mg, 0.242 mmol) in EtOAc (2 mL) at 0° C. was added solution of (1S,8aS)-7,7-diallyl-1-o-tolylhexahydropyrrolo[1,2-a]pyrazin-6(7H)-one (150 mg, 0.484 mmol), DMAP (6.2 mg, 0.05 mmol) and TEA (151 mg, 1.5 mmol) in EtOAc (15 mL). The mixture was stirred for 1.5 h, followed by addition of (R)-1-(3-isopropyl-5-(trifluoromethyl)phenyl)-N-methylethanamine (142 mg, 0.58 mmol) in EtOAc (10 mL) and TEA (151 mg, 1.5 mmol). The reaction was stirred at 50° C. for 48 h and quenched with water. The resulting mixture was extracted with EtOAc. The organic layer was washed with 1 M aqueous HCl solution, dried over anhydrous Na2SO4 and then concentrated in high vacuum. The residue was purified by silica gel chromatography (DCM/MeOH=20/1 to 10/1) to give the title compound (100 mg, yield: 36%) as yellow solid; m/z (ES+): 582 [M+H]+.

Workup

  1. stirringThe reaction was stirred at 50° C. for 48 h
  2. customquenched with water
  3. extractionThe resulting mixture was extracted with EtOAc
  4. washThe organic layer was washed with 1 M aqueous HCl solution
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in high vacuum
  7. customThe residue was purified by silica gel chromatography (DCM/MeOH=20/1 to 10/1)

Sources & evidence

ORD record
ord-d8f4be069c994af8929498e9b02523f1
Source dataset
uspto-grants-2015_11
Patent number
US09181259B2

Reaction notes

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