Potassium Carbonate → 2-[3,5-bis(trifluoromethyl)phenyl]-N-{4-(4-fluoro-2-methylphenyl)-6-[(8S)-8-hydroxyhexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-3-pyridinyl}-N,2-dimethylpropanamide

HRID 2074926Notes

Reaction equation

HRID 2074926 reaction equation
[CH2:1]1[NH:6][CH2:5][CH2:4][N:3]2[CH2:7][CH2:8][C@H:9]([OH:10])[CH:2]12.[F:11][C:12]([F:46])([F:45])[C:13]1[CH:14]=[C:15]([C:23]([CH3:44])([CH3:43])[C:24]([N:26]([C:28]2[CH:29]=[N:30][C:31](Cl)=[CH:32][C:33]=2[C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=2[CH3:41])[CH3:27])=[O:25])[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[F:22][C:19]([F:20])([F:21])[C:17]1[CH:16]=[C:15]([C:23]([CH3:44])([CH3:43])[C:24]([N:26]([C:28]2[CH:29]=[N:30][C:31]([N:6]3[CH2:5][CH2:4][N:3]4[CH2:7][CH2:8][C@H:9]([OH:10])[CH:2]4[CH2:1]3)=[CH:32][C:33]=2[C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=2[CH3:41])[CH3:27])=[O:25])[CH:14]=[C:13]([C:12]([F:46])([F:11])[F:45])[CH:18]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 55300579(8S)-octahydropyrrolo[1,2-a]pyrazin-8-ol

Product 1

HCID 160640392-[3,5-bis(trifluoromethyl)phenyl]-N-{4-(4-fluoro-2-methylphenyl)-6-[(8S)-8-hydroxyhexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-3-pyridinyl}-N,2-dimethylpropanamideYield 26.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (8S)-octahydropyrrolo[1,2-a]pyrazin-8-ol (D71, 32 mg) in methyl sulfoxide (1.2 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 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 by flash chromatography (DCM/MeOH from 100:0 to 95:5) to give the desired compound (18.8 mg) as yellow foam.

Workup

  1. temperatureto cool down to r.t.
  2. extractionThe aqueous phase was extracted with ethyl acetate (3×2.5 mL)
  3. customThe combined organic extracts were dried
  4. concentrationconcentrated in vacuo to a residue which
  5. customwas purified by flash chromatography (DCM/MeOH from 100:0 to 95:5)

Sources & evidence

ORD record
ord-e6262219f4f74072995b88f7944b70ce
Source dataset
uspto-grants-2011_04
Patent number
US07919491B2

Reaction notes

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