m-Chloroperbenzoic acid → N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine

HRID 968667

Reaction equation

HRID 968667 reaction equation
[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)[C:15](I)=[C:11]3[N:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CSC1N=C([Sn](CCCC)(CCCC)CCCC)C=CN=1.[F-].[K+].[CH:48]1([NH:53][C:54]2[N:59]3[N:60]=[C:61](C4C=CC(OC)=CC=4)[CH:62]=[C:58]3N=CC=2)[CH2:52][CH2:51][CH2:50][CH2:49]1.C1(NC2N3N=C(C4C=CC(OC)=CC=4)C(C4C=CN=C(SC)N=4)=C3N=CC=2)CCCC1.ClC1C=C(C=CC=1)C(OO)=O>C(OCC)(=O)C.ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1>[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)[C:15]([C:61]4[CH:62]=[CH:58][N:59]=[C:54]([NH:53][CH:48]5[CH2:49][CH2:50][CH2:51][CH2:52]5)[N:60]=4)=[C:11]3[N:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

11

Reactant 6

HCID 70297m-Chloroperbenzoic acidHCID 522689Potassium FluorideHCID 27632612-(Methylthio)-4-(tributylstannyl)pyrimidineHCID 69489940N-cyclopentyl-2-(4-methoxyphenyl)-3-[2-(methylsulfanyl)pyrimidin-4yl]pyrazolo[1,5-a]pyrimidin-7-amineHCID 69490015N-cyclopentyl-3-iodo-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amineHCID 69491756N-cyclopentyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amine

Product 1

HCID 45485648N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4methoxyphenyl)pyrazolo[1,5-a]pyrimidin-7-amineYield 11%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

N-Cyclopentyl-3-iodo-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyrimidin-7-amine (63 mg, 0.15 mmol), dichlorobis(triphenylphosphine)palladium(II) (25 mg, 0.015 mmol), and 2-(methylsulfanyl)-4-(tributylstannyl)pyrimidine (78 mg, 0.19 mmol) were added to toluene (3 mL) and heated to 110° C. for 16 hours. Additional dichlorobis(triphenylphosphine)palladium(II) (6 mg) was added and the reaction heated to 110° C. for 24 hours. The reaction was allowed to cool to room temperature, diluted with ethyl acetate, poured into 10% aqueous potassium fluoride containing 1% methanol, and stirred for 20 minutes before being extracted with ethyl acetate. The organic phase was concentrated and the residue purified by silica chromatography, eluting with a gradient of 5% to 10% acetone in dichloromethane to yield 25 mg of an approximate 1:1 mixture of N-cyclopentyl-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyrimidin-7-amine and N-cyclopentyl-2-(4-methoxyphenyl)-3-[2-(methylsulfanyl)pyrimidin-4yl]pyrazolo[1,5-α]pyrimidin-7-amine. To a 0° C. solution of this mixture in dichloromethane (1 mL) was added 3-chloroperoxybenzoic acid (0.099 mg, 0.058 mmol). The mixture was allowed to warm to room temperature and stirred for 2 hours. The mixture was diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate, and concentrated. The residue was dissolved in cyclopentylamine and stirred at room temperature for 2.5 hours. The mixture was concentrated and the residue purified by silica chromatography, eluting with a gradient of 5% to 15% acetone in dichloromethane to yield 14 mg (11%) of N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4methoxyphenyl)pyrazolo[1,5-α]pyrimidin-7-amine. 1H NMR (CDCl3):δ 8.37 (d, 1H), 8.26 (d, 1H), 7.67 (d, 2H), 6.99 (d, 2H), 6.50 (d, 1H), 6.11 (d, 1H), 5.01 (m, 1H), 4.09 (m, 1H), 3.90 (s, 3H), 2.20 (m, 2H), 1.75 (m, 14H); MS m/z 470 (M+1).

Workup

  1. temperaturethe reaction heated to 110° C. for 24 hours
  2. temperatureto cool to room temperature
  3. extractionbefore being extracted with ethyl acetate
  4. concentrationThe organic phase was concentrated
  5. customthe residue purified by silica chromatography
  6. washeluting with a gradient of 5% to 10% acetone in dichloromethane
  7. customto yield
  8. temperatureto warm to room temperature
  9. stirringstirred for 2 hours
  10. washwashed with saturated aqueous sodium bicarbonate
  11. concentrationconcentrated
  12. dissolutionThe residue was dissolved in cyclopentylamine
  13. stirringstirred at room temperature for 2.5 hours
  14. concentrationThe mixture was concentrated
  15. customthe residue purified by silica chromatography
  16. washeluting with a gradient of 5% to 15% acetone in dichloromethane

Sources & evidence

ORD record
ord-faadbae44cda4e9fbb1d20e28d49c886
Source dataset
uspto-grants-2007_12
Patent number
US07304068B2

Linked notes

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