Ammonium formate → Tert-butyl 4-[2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl]phenoxy]ethyl]piperazine-1-carboxylate

HRID 2381094Notes

Reaction equation

HRID 2381094 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[N:7]2[N:8]=[C:9]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]4[CH:39]=[CH:38][C:21]([O:22][CH2:23][CH2:24][N:25]5[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]5)=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[CH:10]=[CH:11][C:6]2=[N:5][N:4]=1.C([O-])=O.[NH4+]>[Pd].C(O)C>[F:41][C:2]([F:1])([F:40])[C:3]1[N:7]2[N:8]=[C:9]([N:12]3[CH2:13][CH2:14][CH:15]([C:18]4[CH:19]=[CH:20][C:21]([O:22][CH2:23][CH2:24][N:25]5[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])[CH2:29][CH2:30]5)=[CH:38][CH:39]=4)[CH2:16][CH2:17]3)[CH2:10][CH2:11][C:6]2=[N:5][N:4]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formate2×HCID 66788098Tert-butyl 4-[2-[4-[1-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl]phenoxy]ethyl]piperazine-1-carboxylate

Product 1

HCID 68503507Tert-butyl 4-[2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl]phenoxy]ethyl]piperazine-1-carboxylateYield 81%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

10% Palladium on carbon (0.924 g, 0.87 mmol) was added to tert-butyl 4-[2-[4-[1-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]ethyl]piperazine-1-carboxylate (2.5 g, 4.34 mmol) and ammonium formate (2.74 g, 43.43 mmol) in ethanol (100 mL). The resulting mixture was stirred at 78° C., with further portions of ammonium formate being added every 5 hours until the reaction was complete. The reaction mixture was cooled to room temperature and the catalyst was removed by filtration. The filtrate was evaporated to dryness, redissolved in DCM (100 mL) and the solution was washed with water (100 mL) followed by brine (50 mL), then the solvents were evaporated to afford tert-butyl 4-[2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl]phenoxy]ethyl]piperazine-1-carboxylate (2.020 g, 81%) as a solid.

Workup

  1. additionadded every 5 hours until the reaction
  2. customthe catalyst was removed by filtration
  3. customThe filtrate was evaporated to dryness
  4. dissolutionredissolved in DCM (100 mL)
  5. washthe solution was washed with water (100 mL)
  6. customthe solvents were evaporated

Sources & evidence

ORD record
ord-fb97b0751f3c40438c67463519a8ff39
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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