Cyclopentylamine → 1-[7-(Cyclopentylamino)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone

HRID 861106Notes

Reaction equation

HRID 861106 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C:10]([C:11](=[O:13])[CH3:12])=[C:6]2[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:28]1([NH2:33])[CH2:32][CH2:31][CH2:30][CH2:29]1.C(OCC)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[CH:28]1([NH:33][C:2]2[N:7]3[N:8]=[C:9]([C:14]4[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=4)[C:10]([C:11](=[O:13])[CH3:12])=[C:6]3[CH:5]=[CH:4][CH:3]=2)[CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

9

Reactant 4

HCID 2906CyclopentylamineHCID 3283Diethyl EtherHCID 10796Cesium carbonateHCID 223500511-[7-(Chloro)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone

Product 1

HCID 223500531-[7-(Cyclopentylamino)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanoneYield 97.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 1-[7-(chloro)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone (5.0 g, 16.6 mmol) in toluene (100 mL) was added successively racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (620 mg, 1.0 mmol), cesium carbonate (8.12 g, 24.9 mmol), cyclopentylamine (8.2 mL, 83.1 mmol), and palladium (II) acetate (150 mg, 0.66 mmol). The resulting mixture was stirred at 95° C. for 4 hours, at which time the reaction was judged complete by thin layer chromatography. The solution was cooled to room temperature and diethyl ether and water were added to the reaction mixture. The phases were separated, and the aqueous phase again extracted with diethyl ether. The combined organic phases were dried (magnesium sulfate), filtered and concentrated. The resulting residue was purified by flash chromatography (4:1 hexanes:ethyl acetate) to give 1-[7-(cyclopentylamino)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone (5.66 g, 97%) as a yellow foam. 1H NMR (CDCl3): δ 7.65 (d, 1H), 7.48 (d, 2H), 7.39 (t, 1H), 6.99 (d, 2H), 6.09 (d, 1H), 6.01 (d, 1H), 3.95 (m, 1H), 3.84 (s, 3H), 2.09 (s, 3H), 2.09–2.00 (m, 2H) 1.76–1.22 (m, 6H); MS m/z 350 (M+1).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customThe phases were separated
  3. extractionthe aqueous phase again extracted with diethyl ether
  4. dry with materialThe combined organic phases were dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by flash chromatography (4:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-20e0e0fea7e649e7b2405d9c9fba3cea
Source dataset
uspto-grants-2006_12
Patent number
US07153855B2

Reaction notes

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