Ammonium formate → HCID 46892569, compound

HRID 2381147Notes

Reaction equation

HRID 2381147 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C@@H:8]([CH3:36])[CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([C:23]4[CH:24]=[CH:25][C:26]5[N:27]([C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][N:31]=5)[N:28]=4)[CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[CH2:4][C:3]1=[O:37].C([O-])=O.[NH4+]>C(O)C.[Pd]>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C@@H:8]([CH3:36])[CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([C:23]4[CH2:24][CH2:25][C:26]5[N:27]([C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][N:31]=5)[N:28]=4)[CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[CH2:4][C:3]1=[O:37]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 68501528HCID 68501528, compound

Product 1

HCID 46892569HCID 46892569, compoundYield 44.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
78 °C

Procedure

Palladium (8.22 mg, 0.08 mmol) was added to (S)-1-methyl-4-[1-methyl-2-(4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)ethyl]piperazin-2-one (0.040 g, 0.08 mmol) and ammonium formate (0.146 g, 2.32 mmol) in ethanol (5 mL) at 20° C. The resulting suspension was stirred at 78° C. for 24 hours. The catalyst was filtered off through a pad of diatomaceous earth and the filtrate was concentrated under reduced pressure to give a yellow gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Pure fractions were evaporated to dryness to afford (S)-1-methyl-4-[1-methyl-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 (0.018 g, 44.8%), which was shown by chiral hplc to correspond to the first eluting isomer obtained in Example 55.1.

Workup

  1. filtrationThe catalyst was filtered off through a pad of diatomaceous earth
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customto give a yellow gum
  4. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM
  5. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-e6555bdad0e54a9090bdd9229f159d7e
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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