N-Acetyl-4-piperidone → HCID 178473837, compound

HRID 707332Notes

Reaction equation

HRID 707332 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][C@H:8]1[CH2:11][C@H:10]([N:12]2[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[C:14]([NH2:21])=[N:13]2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:23]([N:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1)(=[O:25])[CH3:24].C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(O)(=O)C.C(OCC)(=O)C.O>[C:1]([O:5][C:6](=[O:22])[NH:7][C@H:8]1[CH2:11][C@H:10]([N:12]2[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[C:14]([NH:21][CH:29]3[CH2:30][CH2:31][N:26]([C:23](=[O:25])[CH3:24])[CH2:27][CH2:28]3)=[N:13]2)[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 4

HCID 122563N-Acetyl-4-piperidoneHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 178454109HCID 178454109, compound

Product 1

HCID 178473837HCID 178473837, compoundYield 45.2%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Tert-butyl(trans-3-(3-amino-1H-pyrazolo[3,4-b]pyridin-1-yl)cyclobutyl)carbamate (from example 113, step 2, 0.210 g, 0.692 mmol) was dissolved in methanol (4 mL) and acetic acid (3 drops). 1-Acetyl-4-piperidone (0.100 ml, 0.812 mmol) was added and the mixture heated at 60° C. for 1 hour. The solution was cooled and sodium cyanoborohydride (0.065 g, 1.034 mmol) was added. The reaction was stirred for 14 hours at room temperature. Saturated sodium bicarbonate (10 mL), water (50 mL) and ethyl acetate (100 mL) were added and the mixture stirred for 20 minutes. The phases were separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. Purification using silica chromatography (0-10% methanol in dichloromethane gradient) gave the desired tert-butyl(trans-3-(3-((1-acetylpiperidin-4-yl)amino)-1H-pyrazolo[3,4-b]pyridin-1-yl)cyclobutyl)carbamate (0.134 g, 0.313 mmol, 45.2% yield).

Workup

  1. temperatureThe solution was cooled
  2. stirringthe mixture stirred for 20 minutes
  3. customThe phases were separated
  4. dry with materialthe organic dried with magnesium sulfate
  5. custombefore evaporating to dryness under reduced pressure
  6. customPurification

Sources & evidence

ORD record
ord-6a3870f68e604a28bbb5b3c672efdf2b
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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