Triphosgene → HCID 71715371, compound

HRID 711348Notes

Reaction equation

HRID 711348 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[C:13]1([CH3:29])[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C@@H:19]1[NH:24][CH2:23][CH2:22][N:21]2[C:25](=[O:28])[CH2:26][CH2:27][C@@H:20]12.[CH3:30][NH:31][C@@H:32]([C:34]1[CH:39]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:37]=[C:36]([CH3:44])[CH:35]=1)[CH3:33]>CCOC(C)=O.CN(C1C=CN=CC=1)C>[CH3:30][N:31]([C@@H:32]([C:34]1[CH:39]=[C:38]([C:40]([F:41])([F:43])[F:42])[CH:37]=[C:36]([CH3:44])[CH:35]=1)[CH3:33])[C:5]([N:24]1[CH2:23][CH2:22][N:21]2[C:25](=[O:28])[CH2:26][CH2:27][C@H:20]2[C@@H:19]1[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH3:29])=[O:11]

Participants

6

Reactant 3

HCID 94429TriphosgeneHCID 89768238HCID 89768238, compoundHCID 89771121HCID 89771121, compound

Product 1

HCID 71715371HCID 71715371, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent3×

Procedure

To a solution of triphosgene (254 mg, 0.87 mmol) in EtOAc (5 mL) at 0° C. was added solution of (1S,8aS)-1-o-tolylhexahydropyrrolo[1,2-a]pyrazin-6(7H)-one (400 mg, 1.73 mmol), DMAP (21 mg, 0.173 mmol) and TEA (524 mg, 5.19 mmol in EtOAc (5 mL). The mixture was stirred for 1.5 h, followed by addition of (R)-N-methyl-1-(3-methyl-5-(trifluoromethyl)phenyl)ethanamine (563 mg, 2.6 mmol) in EtOAc (2 mL) and TEA (524 mg, 5.19 mmol). The reaction was stirred at 50° C. for 48 h and quenched with water. The resulting mixture was extracted with EtOAc and 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 (350 mg, yield: 85%). 1H NMR (400 MHz, CDCl3) δ ppm 7.32 (s, 1H), 7.25 (d, J=8.0 Hz, 1H), 7.19 (d, J=7.4 Hz, 2H), 7.14 (ddd, J=17.5, 10.0, 4.2 Hz, 2H), 7.00 (s, 1H), 5.48 (q, J=6.9 Hz, 1H), 4.22 (m, 2H), 3.71 (dd, J=17.0, 7.3 Hz, 1H), 3.29 (d, J=11.8 Hz, 1H), 3.11 (td, J=12.4, 2.7 Hz, 1H), 2.95 (td, J=11.9, 3.2 Hz, 1H), 2.64 (s, 3H), 2.54 (s, 3H), 2.48 (m, 2H), 2.34 (s, 3H), 1.87 (m, 1H), 1.67 (ddd, J=17.1, 13.1, 9.4 Hz, 1H), 1.37 (d, J=6.7 Hz, 3H); m/z (ES+): 474 [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-81cca7364dea4663b41a502d7629f370
Source dataset
uspto-grants-2015_11
Patent number
US09181259B2

Reaction notes

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