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Potassium Carbonate → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-((3S,5S)-3,5-dimethylmorpholino)-2-butynyl]-2-[(1H-indol-3-yl)methyl]piperazine

HRID 584244
Notes
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Reaction equation

HRID 584244 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]1[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:7].[CH3:33][C@H:34]1[CH2:39][O:38][CH2:37][C@H:36]([CH3:40])[N:35]1[CH2:41][C:42]#[C:43][CH2:44]Cl.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:30][C:27]([F:28])([F:29])[C:25]1[CH:24]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:31])[F:32])[CH:26]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:44][C:43]#[C:42][CH2:41][N:35]2[C@@H:36]([CH3:40])[CH2:37][O:38][CH2:39][C@@H:34]2[CH3:33])[CH2:10][C@H:9]1[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:7]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 10972505(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)piperazineHCID 57008703(3S,5S)-3,5-dimethyl-4-(4-chloro-2-butynyl)morpholine

Product 1

HCID 57023434(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-((3S,5S)-3,5-dimethylmorpholino)-2-butynyl]-2-[(1H-indol-3-yl)methyl]piperazine

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent

Conditions

Temperature
60 °C

Procedure

A mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[(1H-indol-3-yl)methyl]piperazine (0.20 g), (3S, 5S)-3,5-dimethyl-4-(4-chloro-2-butynyl)morpholine (0.11 g) and potassium carbonate (0.31 g) in N,N-dimethylformamide (4 ml) was stirred at 60° C. for 3 hours. After cooling, the solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and sodium hydrogen carbonate solution. The organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel with 3% of methanol in ethyl acetate as an eluent to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-((3S,5S)-3,5-dimethylmorpholino)-2-butynyl]-2-[(1H-indol-3-yl)methyl]piperazine. It was dissolved in ethyl acetate and the solution was added 4N hydrogen chloride in ethyl acetate. The mixture was evaporated in vacuo and the residue was triturated with isopropyl ether to give (2R)-1-[3,5-bis-trifluoromethyl)benzoyl]-4-[4-((3S,5S)-3,5-dimethylmorpholino)-2-butynyl]-2-[(1H-indol-3-yl)methyl]piperazine dihydrochloride (0.11 g).

Workup

  1. temperatureAfter cooling
  2. customthe solvent was removed under reduced pressure
  3. customthe residue was partitioned between ethyl acetate and sodium hydrogen carbonate solution
  4. customThe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography on silica gel with 3% of methanol in ethyl acetate as an eluent

Sources & evidence

ORD record
ord-670dd197d36141fbb57bdd016c128acd
Source dataset
uspto-grants-2005_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06924278B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes