Sodium Carbonate → tert-butyl 2-(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)ethylcarbamate

HRID 1984399

Reaction equation

HRID 1984399 reaction equation
Br[C:2]1[C:3]([C:20]#[N:21])=[N:4][N:5]([CH2:17][CH2:18][CH3:19])[C:6]=1[CH2:7][CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13].Cl.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(O)CC>[NH2:21][C:20]1[C:3]2=[N:4][N:5]([CH2:17][CH2:18][CH3:19])[C:6]([CH2:7][CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[C:2]2[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N:23]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 164270902-Aminophenylboronic acid hydrochlorideHCID 66958960tert-butyl 2-(4-bromo-3-cyano-1-propyl-1H-pyrazol-5-yl)ethylcarbamate

Product 1

HCID 66958848tert-butyl 2-(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)ethylcarbamateYield 44.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

A flask containing a mixture of tert-butyl 2-(4-bromo-3-cyano-1-propyl-1H-pyrazol-5-yl)ethylcarbamate (15.8 g, 44.2 mmol), 2-aminophenylboronic acid hydrochloride (11.5 g, 66.3 mmol), triphenylphosphine (1.04 g, 3.98 mmol), palladium (II) acetate (299 mg, 1.33 mmol), 2 M aqueous sodium carbonate (67 mL, 133 mmol), 1-propanol (77.4 mL), and water (15.5 mL) was heated overnight under a nitrogen atmosphere in a 100° C. oil bath. The reaction was allowed to cool to ambient temperature and water (300 mL) was added. The mixture was extracted with chloroform, dried over magnesium sulfate, filtered, and concentrated to provide an oil that was purified twice by flash chromatography (silica gel, first column: eluted sequentially with 0-10% CMA in chloroform, and then 25% CMA in chloroform; second column: gradient elution with 50-60% ethyl acetate in hexanes) to yield 7.3 g of tert-butyl 2-(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)ethylcarbamate as a yellow resin.

Workup

  1. additionA flask containing
  2. temperatureto cool to ambient temperature
  3. extractionThe mixture was extracted with chloroform
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto provide an oil that
  8. customwas purified twice by flash chromatography (silica gel, first column
  9. washeluted sequentially with 0-10% CMA in chloroform
  10. washsecond column: gradient elution with 50-60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3f3128f1e546428fa7c8e3062feb855e
Source dataset
uspto-grants-2009_06
Patent number
US07544697B2

Linked notes

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