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

HRID 2381086Notes

Reaction equation

HRID 2381086 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[N:7]2[N:8]=[C:9]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]4[CH:40]=[CH:39][C:21]([O:22][CH2:23][CH2:24][CH2:25][N:26]5[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]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:42][C:2]([F:1])([F:41])[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][CH2:25][N:26]5[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[CH2:28][CH2:27]5)=[CH:39][CH:40]=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 68500015Tert-butyl 4-[3-[4-[1-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]propyl]piperazine-1-carboxylate

Product 1

HCID 68500212Tert-butyl 4-[3-[4-(1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl]phenoxy]propyl]piperazine-1-carboxylateYield 88%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

10% Palladium on carbon (0.859 g, 0.81 mmol) was added to tert-butyl 4-[3-[4-[1-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]propyl]piperazine-1-carboxylate (2.38 g, 4.04 mmol) and ammonium formate (2.55 g, 40.36 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, the residue was re-dissolved in DCM (100 mL) and the solution was washed with water (50 mL) and brine (50 mL). The solvents were evaporated to give tert-butyl 4-[3-[4-(1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl]phenoxy]propyl]piperazine-1-carboxylate (2.090 g, 88%) 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. dissolutionthe residue was re-dissolved in DCM (100 mL)
  5. washthe solution was washed with water (50 mL) and brine (50 mL)
  6. customThe solvents were evaporated

Sources & evidence

ORD record
ord-d6b463e0557d4f0b8f7e93efb86b69b8
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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