HCID 10759534, compound → HCID 54179169, compound

HRID 361828Notes

Reaction equation

HRID 361828 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH3:25])[C:15]2[C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=[CH:17][N:16]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1>CO.O.[Pd]>[CH3:25][N:14]([CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)[C:15]1[C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=[CH:17][N:16]=1

Participants

4

Reactant 1

HCID 10759534HCID 10759534, compound

Product 1

HCID 54179169HCID 54179169, compound

Reagents, catalysts & solvents 2

HCID 23219155Palladium hydrateCatalystHCID 887MethanolSolvent

Procedure

A mixture of 1-benzyl-4-[N-methyl-N-(3-methoxycarbonyl-2-pyridyl)amino]piperidine (EXAMPLE 136, 250 mg) and palladium hydroxide-on-carbon (20%, 45% moisture, 100 mg) in methanol (14 ml) is shaken on a Parr hydrogenation apparatus under a hydrogen atmosphere at 40 psi for 2 hrs and at 28 psi for 16 hrs. The catalyst is then removed by filtration through diatomaceous earth and the filtrate is concentrated under reduced pressure and flushed through a short pad of silica gel (70-230 mesh, 5 g), eluting with a gradient of methanol/methylene chloride (5/95-20/80). Pooling of fractions with an Rf =0.06 by TLC (methanol/chloroform, 20/80) and removal of solvent under reduced pressure gives 4-[N-methyl-N-(3-methoxycarbonyl-2-pyridyl)amino]piperidine. To a flame-dried flask under nitrogen is added 5-(methanesulfonylamino)indolyl-2-carboxylic acid (135 mg), 1,1-carbonyldiimidazole (754 mg) and dry tetrahydrofuran (2.5 ml) and the mixture is stirred at 20°-25° for 1 hr. Then a mixture of the debenzylated intermediate 4-[N-methyl-N-(3-methoxycarbonyl-2-pyridyl)amino]piperidine (110 mg), in dry tetrahydrofuran (3 ml) is added and the resultant mixture is stirred at 20°-25° for 20 hrs and concentrated under reduced pressure to remove solvent. The residue is diluted with methylene chloride (20 ml), washed with water (5 ml), saturated aqueous sodium bicarbonate (5 ml) and saline (5 ml), dried over sodium sulfate, concentrated under reduced pressure and chromatographed (silica gel, 230-400 mesh, 25 g; eluting with a gradient of methanol/methylene chloride (1/99-3/97)). Pooling of fractions with an Rf =0.28 by TLC (methanol/chloroform, 5/95) and removal of solvent under reduced pressure gives the title compound, mp 223°-224°.

Workup

  1. customThe catalyst is then removed by filtration through diatomaceous earth
  2. concentrationthe filtrate is concentrated under reduced pressure
  3. customflushed through a short pad of silica gel (70-230 mesh, 5 g)
  4. washeluting with a gradient of methanol/methylene chloride (5/95-20/80)
  5. customPooling of fractions with an Rf =0.06 by TLC (methanol/chloroform, 20/80) and removal of solvent under reduced pressure

Sources & evidence

ORD record
ord-87013185a03e4f829f741854b2ac5714
Source dataset
uspto-grants-1999_02
Patent number
US05866589

Reaction notes

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