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

HRID 2381136Notes

Reaction equation

HRID 2381136 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[CH:31]=[CH: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.[CH3:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][C:45]1=[O:50]>CC(N(C)C)=O>[CH3:43][N:44]1[CH2:49][CH2:48][N:47]([CH2:15][CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]([CH:24]3[CH2:25][CH2:26][N:27]([C:30]4[CH:31]=[CH:32][C:33]5[N:34]([C:36]([C:39]([F:40])([F:41])[F:42])=[N:37][N:38]=5)[N:35]=4)[CH2:28][CH2:29]3)=[CH:22][CH:23]=2)[CH2:46][C:45]1=[O:50]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 43990421-Methylpiperazin-2-oneHCID 866466942-(4-{1-[3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate

Product 1

HCID 498057211-Methyl-4-[2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-oneYield 68.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

DIPEA (15.27 mL, 87.69 mmol) was added to 2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl methanesulfonate (14.19 g, 29.23 mmol) and 1-methylpiperazin-2-one (CAS 59702-07-7, 3.67 g, 32.15 mmol) in DMA (70 mL). The resulting solution was stirred at 110° C. for 1 hour. The reaction mixture was cooled to room temperature, absorbed onto silica, evaporated to dryness and then purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM. Pure fractions were evaporated and the resulting gum was scratched with ether until solid. The solid was stirred in ether (100 mL) for 4 hours then collected by filtration and dried to give 1-methyl-4-[2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-one (10.08 g, 68.5%) as a solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customabsorbed onto silica
  3. customevaporated to dryness
  4. custompurified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM
  5. customPure fractions were evaporated
  6. stirringThe solid was stirred in ether (100 mL) for 4 hours
  7. filtrationthen collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-5e10f74287f442169ef830d8a0eb204f
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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