Cyclopentylamine → N-Cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-8-amine

HRID 456693

Reaction equation

HRID 456693 reaction equation
Cl[C:2]1[C:3]2[N:4]([C:8]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)[N:19]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=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[C:3]3[N:4]([C:8]([C:18]4[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]5[CH2:29][CH2:28][CH2:27][CH2:26]5)[N:19]=4)=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[N:10]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:92][CH2:91][CH2:90][CH2:89]1

Participants

8

Reactant 5

HCID 2906CyclopentylamineHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 102014694-[8-Chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-cyclopentylpyrimidin-2-amine

Product 1

HCID 10161456N-Cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-8-amineYield 55%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-[8-chloro-2-(4-fluorophenyl)imidazo[1,2-α]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (200 mg, 0.49 mmol) in cyclopentylamine (10 mL) was added, successively, racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (91 mg, 0.15 mmol), cesium carbonate (0.24 g, 0.7 mmol) and palladium(II) acetate (22 mg, 0.1 mmol). The resulting mixture was heated in a sealed tube at 100° C. for 18 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. The phases were separated and the organic layer was washed with water and brine. The combined organics were dried (magnesium sulfate), filtered and concentrated to a solid. This solid was purified by silica gel chromatography (1:1 hexanes:ethyl acetate) to give N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)imidazo[1,2-α]pyridin-8-amine (120 mg, 55%) as a solid. 1H NMR (CDCl3) δ 8.80 (d, 1H), 8.06 (d, 1H), 7.62 (q, 2H), 7.10 (t, 2H), 6.76 (t, 1H), 6.34 (d, 1H), 6.27 (d, 1H), 5.22 (d, 2H), 4.34 (m, 1H), 3.93 (m, 1H), 2.0–2.1 (m, 4H), 1.4–1.9 (m, 12H); 19F NMR (CDCl3) δ −113.9; MS m/z 457 (M+1).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customThe phases were separated
  3. washthe organic layer was washed with water and brine
  4. dry with materialThe combined organics were dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated to a solid
  7. customThis solid was purified by silica gel chromatography (1:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-f800a20d6bfc415b8df42aaa962eac75
Source dataset
uspto-grants-2007_03
Patent number
US07186714B2

Linked notes

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