Potassium Carbonate → 2-[3,5-Bis(trifluoromethyl)phenyl]-n{4-(4-fluoro-2-methylphenyl)-6-[8a-(hydroxymethyl)hexahydropyrrolo[1,2-a]pyrazin-2(1h)-yl]-3-pyridinyl}-n,2-dimethylpropanamide

HRID 2074925Notes

Reaction equation

HRID 2074925 reaction equation
[CH2:1]1[NH:6][CH2:5][CH2:4][N:3]2[CH2:7][CH2:8][CH2:9][C:2]12[CH2:10][OH:11].[F:12][C:13]([F:47])([F:46])[C:14]1[CH:15]=[C:16]([C:24]([CH3:45])([CH3:44])[C:25]([N:27]([C:29]2[CH:30]=[N:31][C:32](Cl)=[CH:33][C:34]=2[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[CH3:42])[CH3:28])=[O:26])[CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[F:23][C:20]([F:21])([F:22])[C:18]1[CH:17]=[C:16]([C:24]([CH3:45])([CH3:44])[C:25]([N:27]([C:29]2[CH:30]=[N:31][C:32]([N:6]3[CH2:5][CH2:4][N:3]4[CH2:7][CH2:8][CH2:9][C:2]4([CH2:10][OH:11])[CH2:1]3)=[CH:33][C:34]=2[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[CH3:42])[CH3:28])=[O:26])[CH:15]=[C:14]([C:13]([F:47])([F:12])[F:46])[CH:19]=1

Participants

6

Reactant 3

HCID 11430Potassium Carbonate2×HCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 45122045(Octahydropyrrolo[1,2-a]pyrazin-8a-yl)methanol

Product 1

HCID 160640382-[3,5-Bis(trifluoromethyl)phenyl]-n{4-(4-fluoro-2-methylphenyl)-6-[8a-(hydroxymethyl)hexahydropyrrolo[1,2-a]pyrazin-2(1h)-yl]-3-pyridinyl}-n,2-dimethylpropanamideYield 10.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of hexahydropyrrolo[1,2-a]pyrazin-8a(6H)-ylmethanol (D67, 35 mg) in methyl sulfoxide (1.5 mL), 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide [WO 2005/002577] (60 mg) and potassium carbonate (63 mg) were added. The resulting mixture was heated at 150° C. for 24 hours. The mixture was allowed to cool down to r.t and further D67 (17 mg) and potassium carbonate (15 mg) were added. The resulting mixture was heated at 150° C. for further 8 hours and then it was allowed to cool to r.t. and diluted with water (2 mL). The aqueous phase was extracted with ethyl acetate (3×2.5 mL). The combined organic extracts were dried and concentrated in vacuo to a residue which was purified twice by flash chromatography (first purification: EtOAc/Cycl from 80/20 to 100:0 then DCM/MeOH 95:5. Second purification: DCM/MeOH 98:2) to give the desired compound (7.7 mg) as yellow foam.

Workup

  1. temperatureto cool down
  2. temperatureThe resulting mixture was heated at 150° C. for further 8 hours
  3. temperatureto cool to r.t.
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×2.5 mL)
  5. customThe combined organic extracts were dried
  6. concentrationconcentrated in vacuo to a residue which
  7. customwas purified twice by flash chromatography (
  8. customfirst purification
  9. customSecond purification

Sources & evidence

ORD record
ord-1ef9d2b7fb164b6bba20dd80dede7d92
Source dataset
uspto-grants-2011_04
Patent number
US07919491B2

Reaction notes

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