Cyclopentylamine → N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)-pyrazolo[1,5-a]pyridin-5-amine

HRID 1796569Notes

Reaction equation

HRID 1796569 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)[N:12]=3)=[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+].C(OCC)(=O)C.[CH:88]1([NH2:93])[CH2:92][CH2:91][CH2:90][CH2:89]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH:88]1([NH:93][C:2]2[CH:7]=[CH:6][N:5]3[N:8]=[C:9]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[C:10]([C:11]4[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]5[CH2:22][CH2:21][CH2:20][CH2:19]5)[N:12]=4)=[C:4]3[CH:3]=2)[CH2:92][CH2:91][CH2:90][CH2:89]1

Participants

8

Reactant 5

HCID 2906CyclopentylamineHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 102231334-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine

Product 1

HCID 10276099N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)-pyrazolo[1,5-a]pyridin-5-amineYield 70%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (0.1 g, 0.25 mmol) in cyclopentylamine (5 mL) was added racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (46 mg, 0.08 mmol), cesium carbonate (120 mg, 0.38 mmol) and palladium (II) acetate (11 mg, 0.05 mmol). The resulting mixture was stirred at 80° C. for 24 hours, at which time the reaction was judged complete by thin layer chromatography. The solution was cooled to room temperature and ethyl acetate and water were added to the reaction mixture. The phases were separated, and the aquous phase again extracted with ethyl acetate. The combined organics were dried (magnesium sulfate), filtered and concentrated. The resulting residue was purified by flash chromatography (1:1 hexanes-ethyl acetate) to give N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-amine (78 mg, 70%) as a white solid. 1H-NMR (CDCl3): δ 8.16 (d, 1H), 7.95 (d, 1H), 7.58 (q, 2H), 7.38 (d, 1H), 7.12 (t, 2H), 6.24 (dd, 1H), 6.20 (d, 1H), 5.05 (d, 1H), 4.40 (m, 1H), 4.13 (m, 1H), 3.89 (m, 1H), 1.5–2.2 (m, 16H);19F-NMR (CDCl3): δ −113.7; MS m/z 457 (M+1).

Workup

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

Sources & evidence

ORD record
ord-d9599204e3bf4df4b4204062645d2000
Source dataset
uspto-grants-2006_04
Patent number
US07030134B2

Reaction notes

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