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

HRID 724002Notes

Reaction equation

HRID 724002 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]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:4]2[CH:3]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:74]1([NH2:79])[CH2:78][CH2:77][CH2:76][CH2:75]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(OCC)C>[CH:74]1([NH:79][C:2]2[CH:7]=[CH:6][N:5]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:4]3[CH:3]=2)[CH2:78][CH2:77][CH2:76][CH2:75]1

Participants

9

Reactant 4

HCID 2906CyclopentylamineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 693562251-[5-(Chloro)-2-(4-methoxyphenyl) pyrazolo[1,5-alpha]pyridin-3-yl]ethanone

Product 1

HCID 114509291-[5-(Cyclopentylamino)-2-(4-methoxyphenyl) pyrazolo[1,5-alpha]pyridin-3-yl]ethanoneYield 56%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 1-[5-(chloro)-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyridin-3-yl]ethanone (1.77 g, 5.88 mmol) in toluene (60 mL) was added successively racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (220 mg, 0.35 mmol), cesium carbonate (2.88 g, 8.83 mmol), cyclopentylamine (2.9 mL, 29.4 mmol), and palladium (II) acetate (53 mg, 0.24 mmol). The resulting mixture was stirred at 95° C. for 3 days, 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 (3:2 hexanes:ethyl acetate) to give 1-[5-(cyclopentylamino)-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyridin-3-yl]ethanone (1.14 g, 56%) as a yellow solid. 1H NMR (CDCl3): δ 8.19 (d, 1H), 7.52 (d, 2H), 7.45 (d, 1H), 7.03 (d, 2H), 6.35 (dd, 1H), 4.15 (broad s, 1H), 3.98 (m, 1H), 3.91 (s, 3H), 2.21–2.15 (m, 2H), 2.11 (s, 3H), 1.79–1.54 (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 (3:2 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-798574e4b81f42e4bc868de66e595999
Source dataset
uspto-grants-2006_11
Patent number
US07141569B2

Reaction notes

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