Cesium carbonate → 2-[3,5-Bis(trifluoromethyl)phenyl]-N-{4-(4-fluoro-2-methylphenyl)-6-[(8aR)-3-oxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-3-pyridinyl}-N,2-dimethylpropanamide

HRID 421252Notes

Reaction equation

HRID 421252 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21](Cl)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:37]1[NH:42][C:41](=[O:43])[CH2:40][N:39]2[CH2:44][CH2:45][CH2:46][C@H:38]12.CN(C)CN.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Cu](I)I>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:42]3[C:41](=[O:43])[CH2:40][N:39]4[CH2:44][CH2:45][CH2:46][C@@H:38]4[CH2:37]3)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5250464Methanediamine, N,N-dimethyl-HCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 55300705(R)-Hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one

Product 1

HCID 160636852-[3,5-Bis(trifluoromethyl)phenyl]-N-{4-(4-fluoro-2-methylphenyl)-6-[(8aR)-3-oxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-3-pyridinyl}-N,2-dimethylpropanamideYield 50.4%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

The title compound was prepared starting from 100 mg (0.187 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 79 mg (0.563 mmol) of (8aR)-hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one (D14), 72 mg of copper iodide (0.378 mmol), 40 μl (0.375 mmol) of N,N-dimethylmethanediamine, 112.4 mg (0.375 mmol) of cesium carbonate; the reagents were dissolved in 4 ml of dioxane and heated at 80° C. for 4 h and then at 120° C. overnight. The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 60 mg of the title compound as pale yellow solid.

Workup

  1. customThe title compound was prepared
  2. customat 120° C.
  3. customovernight
  4. customThe crude material was purified on SPE cartridge (Silica)
  5. washeluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Sources & evidence

ORD record
ord-7d928706fc824f4899f2f5104ca48023
Source dataset
uspto-grants-2012_01
Patent number
US08097618B2

Reaction notes

Loading…