Potassium Carbonate → HCID 70981018, compound

HRID 1475522Notes

Reaction equation

HRID 1475522 reaction equation
Br[CH2:2][C:3](Cl)=[O:4].[CH2:6]([C:13]1[N:18]=[CH:17][C:16]2[C:19]([CH3:23])([CH3:22])[CH2:20][NH:21][C:15]=2[CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[F:24][C:25]([F:33])([F:32])[CH:26]1[CH2:31][NH:30][CH2:29][CH2:28][NH:27]1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CCOC(C)=O.CO.C(#N)C.O>[CH2:6]([C:13]1[N:18]=[CH:17][C:16]2[C:19]([CH3:23])([CH3:22])[CH2:20][N:21]([C:3](=[O:4])[CH2:2][N:30]3[CH2:29][CH2:28][NH:27][CH:26]([C:25]([F:33])([F:32])[F:24])[CH2:31]3)[C:15]=2[CH:14]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 89602Bromoacetyl chlorideHCID 185197252-(Trifluoromethyl)piperazineHCID 70980189HCID 70980189, compound

Product 1

HCID 70981018HCID 70981018, compoundYield 4.6%

Reagents, catalysts & solvents 5

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of bromoacetyl chloride (0.535 g, 3.4 mmol) in DCM (5 mL) was added to a two phase mixture of 6-benzyl-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridine (0.467 g, 1.7 mmol) sodium hydrogen carbonate (1.43 g, 17 mmol), DCM (20 mL) and water (25 mL) with ice cooling over 0.1 h. The mixture was stirred at 0° C. for 2 h then the organic phase was separated and the aqueous phase was extracted with DCM (25 mL). The combined organic phases were dried (Na2SO4) and evaporated in vacuo to give an oil which was purified by chromatography (SiO2, 20-50% EtOAc in petrol) gave an oil which solidified. A mixture of this material (0.081 g, 0.23 mmol) 2-trifluoromethylpiperazine (0.039 g, 0.25 mmol), potassium carbonate (0.064 g, 0.46 mmol) and acetonitrile (2 mL) was stirred at 20° C. for 4 h. The mixture was partitioned between water (30 mL) and DCM (3×20 mL) and the combined extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography (SiO2, 0-20% MeOH in EtOAc), gave impure product and this was followed by further chromatography (SiO2, 0-5% MeOH in EtOAc) then preparative HPLC (basic method) to give the title compound (0.005 g). 1H NMR (Me-d3-OD): 8.24 (1H, s), 7.94 (1H, s), 7.34-7.23 (4H, m), 7.23-7.16 (1H, m), 4.11 (2H, s), 4.03-3.92 (2H, m), 3.45 (3H, s), 3.08 (1H, d), 3.04-2.81 (3H, m), 2.32 (2H, q), 1.42 (6H, s). MS: [M+H]+=433.

Workup

  1. customthe organic phase was separated
  2. extractionthe aqueous phase was extracted with DCM (25 mL)
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. customevaporated in vacuo
  5. customto give an oil which
  6. customwas purified by chromatography (SiO2, 20-50% EtOAc in petrol)
  7. customgave an oil which
  8. stirringwas stirred at 20° C. for 4 h
  9. customThe mixture was partitioned between water (30 mL) and DCM (3×20 mL)
  10. dry with materialthe combined extracts were dried (Na2SO4)
  11. customevaporated in vacuo
  12. customto give an oil

Sources & evidence

ORD record
ord-12dd758a3f924a939e9ce6196bfcafa6
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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