Diisopropylethylamine → 1-Ethyl-4-[2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-one

HRID 2381138Notes

Reaction equation

HRID 2381138 reaction equation
CCN(C(C)C)C(C)C.CS(O[CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH2:31][CH2:32][C:33]4[N:34]([C:36]([C:39]([F:42])([F:41])[F:40])=[N:37][N:38]=4)[N:35]=3)[CH2:26][CH2:25]2)=[CH:20][CH:19]=1)(=O)=O.[CH2:43]([N:45]1[CH2:50][CH2:49][NH:48][CH2:47][C:46]1=[O:51])[CH3:44]>CN(C=O)C.C(Cl)Cl>[CH2:43]([N:45]1[CH2:50][CH2:49][N:48]([CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([CH:24]3[CH2:25][CH2:26][N:27]([C:30]4[CH2:31][CH2:32][C:33]5[N:34]([C:36]([C:39]([F:41])([F:40])[F:42])=[N:37][N:38]=5)[N:35]=4)[CH2:28][CH2:29]3)=[CH:20][CH:19]=2)[CH2:47][C:46]1=[O:51])[CH3:44]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 98773661-Ethylpiperazin-2-oneHCID 866466972-(4-{1-[3-(Trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate

Product 1

HCID 595428461-Ethyl-4-[2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-oneYield 36.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

DIPEA (0.219 mL, 1.23 mmol) was added to 2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate (200 mg, 0.41 mmol) and 1-ethylpiperazin-2-one (52.6 mg, 0.41 mmol) in DMF (5 mL) at 20° C. under nitrogen. The resulting solution was stirred at 110° C. for 3 hours and the solvent was removed in vacuo to give an orange gum, which was dissolved in DCM (100 mL) and the solution washed with water (100 mL). The organic layer was passed through a phase separating cartridge and then evaporated to dryness to give an orange gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in isohexane then 10% methanolic ammonia in EtOAc. Pure fractions were evaporated to dryness to afford a yellow gum, which was triturated with ether to give 1-ethyl-4-[2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-one (77 mg, 36.1%) as a white solid.

Workup

  1. customthe solvent was removed in vacuo
  2. customto give an orange gum, which
  3. washthe solution washed with water (100 mL)
  4. customseparating cartridge
  5. customevaporated to dryness
  6. customto give an orange gum
  7. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in isohexane
  8. customPure fractions were evaporated to dryness
  9. customto afford a yellow gum, which
  10. customwas triturated with ether

Sources & evidence

ORD record
ord-3d4108b6b7ad4f3cbcde4f526be02555
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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