Ethyl Acetate → tert-butyl 3-(9-isopropyl-6-((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)piperidine-1-carboxylate

HRID 928171Notes

Reaction equation

HRID 928171 reaction equation
[CH:1]([N:4]1[CH:12]=[N:11][C:10]2[C:5]1=[N:6][C:7]([C:20]1[CH2:21][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23][CH2:24][CH:25]=1)=[N:8][C:9]=2[NH:13][C:14]1[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=1)([CH3:3])[CH3:2].C([O-])=O.[NH4+].C(OCC)(=O)C>C(O)C.[Pd]>[CH:1]([N:4]1[CH:12]=[N:11][C:10]2[C:5]1=[N:6][C:7]([CH:20]1[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[CH2:21]1)=[N:8][C:9]=2[NH:13][C:14]1[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=1)([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 2723923Ammonium formateHCID 118073695tert-butyl 3-(9-isopropyl-6((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 118073533tert-butyl 3-(9-isopropyl-6-((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)piperidine-1-carboxylateYield 75.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of tert-butyl 3-(9-isopropyl-6-((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (821 mg, 1.87 mmol) in ethanol (35 mL) was degassed with nitrogen and to this was added 10%-Pd/C (150 mg), and ammonium formate (650 mg, 10 mmol). The resulting mixture was stirred and heated at 60° C. for 3 hr. The reaction was cooled to ambient temperature and the catalyst was removed by filtration. The filtrate was evaporated to give a residue, which was taken into ethyl acetate (100 mL) and the solution washed with water (30 mL), brine (30 mL), dried over Na2SO4 and evaporated to give a residue that was purified via flash chromatography with a gradient from 100% heptane to 100% ethyl acetate to afford the title compound (620 mg), which was used in the following step.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customthe catalyst was removed by filtration
  3. customThe filtrate was evaporated
  4. customto give a residue, which
  5. washthe solution washed with water (30 mL), brine (30 mL)
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customto give a residue that
  9. customwas purified via flash chromatography with a gradient from 100% heptane to 100% ethyl acetate

Sources & evidence

ORD record
ord-35521c452128458388cc632c2058194a
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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