Ethyl Acetate → HCID 58504673, compound

HRID 2367642Notes

Reaction equation

HRID 2367642 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([Cl:9])[N:3]=1.[CH:10]1([NH:16][C:17]([CH:19]2[CH2:24][CH2:23][CH:22]([C:25]([F:28])([F:27])[F:26])[NH:21][CH2:20]2)=[O:18])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.CCN(C(C)C)C(C)C.CCOC(C)=O>O1CCOCC1>[CH:10]1([NH:16][C:17]([CH:19]2[CH2:24][CH2:23][CH:22]([C:25]([F:28])([F:26])[F:27])[N:21]([C:6]3[CH:5]=[C:4]([Cl:9])[N:3]=[C:2]([Cl:1])[N:7]=3)[CH2:20]2)=[O:18])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 773782,4,6-TrichloropyrimidineHCID 81531DiisopropylethylamineHCID 58504410HCID 58504410, compound

Product 1

HCID 58504673HCID 58504673, compoundYield 35.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2,4,6-trichloropyrimidine (0.18 mL, 1.59 mmol) and N-cyclohexyl-6-(trifluoromethyl)-3-piperidinecarboxamide (0.5 g, 1.588 mmol) in 1,4-dioxane (15 mL) was added Hunig's base (0.56 mL, 3.18 mmol), and the reaction mixture was stirred over the weekend (3 days) at 80° C. into a sealed tube. Approximately 35% starting material was remaining. The temperature was increased to 140° C., and the reaction mixture was stirred at this temperature for 3 hours. The reaction was then heated for 1 hour at 160° C. Since there was still remaining starting material, the reaction was stirred overnight at 140° C. The reaction mixture was poured onto water and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100% Hexanes to 50% EtOAc in Hexanes) afforded the title compound (239 mg) as a white solid, and the corresponding regioisomer (196 mg) as a white solid. LC-MS (ES) m/z=425, 427 [M+H]+.

Workup

  1. temperatureThe temperature was increased to 140° C.
  2. stirringthe reaction mixture was stirred at this temperature for 3 hours
  3. temperatureThe reaction was then heated for 1 hour at 160° C
  4. stirringthe reaction was stirred overnight at 140° C
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-8a39818bf5bf4852a62ef32ab8fed3bd
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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