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

HRID 1295880Notes

Reaction equation

HRID 1295880 reaction equation
Cl[C:2]1[C:3]2[N:4]([C:8]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28]C=4)[N:20]=3)=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[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:90]1([NH2:95])[CH2:94][CH2:93][CH2:92][CH2:91]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH:90]1([NH:95][C:2]2[C:3]3[N:4]([C:8]([C:19]4[CH:24]=[CH:23][N:22]=[C:21]([NH:25][CH:26]5[CH2:31][CH2:30][CH2:29][CH2:28]5)[N:20]=4)=[C:9]([C:11]4[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=4)[N:10]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:94][CH2:93][CH2:92][CH2:91]1

Participants

8

Reactant 5

HCID 2906CyclopentylamineHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 102741414-[8-chloro-2-(3-methoxyphenyl)imidazo[1,2-alpha]pyridin-3-yl]-N-phenylpyrimidin-2-amine

Product 1

HCID 10139996N-Cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(3-methoxyphenyl)imidazo[1,2-a]pyridin-8-amineYield 31%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 4-[8-chloro-2-(3-methoxyphenyl)imidazo[1,2-α]pyridin-3-yl]-N-phenylpyrimidin-2-amine (162 mg, 0.39 mmol) in cyclopentylamine (5 mL) was added, successively, racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (15.3 mg, 0.02 mmol), cesium carbonate (376 mg, 1.15 mmol) and palladium (II) acetate (3.5 mg, 0.015 mmol). The resulting mixture was heated in a sealed tube at 150° 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. The phases were separated and the organic layer was washed with water and brine. The combined organics were dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography (2:1 hexanes-ethyl acetate) to give N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(3-methoxyphenyl)imidazo[1,2-α]pyridin-8-amine (55 mg, 31%) as a white solid. 1H NMR (CDCl3): δ 8.90 (m, 1 H), 8.08 (d, 1 H), 7.37–7.22 (m, 2 H), 6.96 (m, 1 H), 6.79 (t, 1 H), 6.43 (d, 1 H), 6.30 (d, 1 H), 5.40 (d, 1 H), 5.31 (d, 1 H), 4.37 (m, 1 H), 3.94 (m, 1 H), 3.85 (s, 3 H), 2.14–2.07 (m, 4 H), 1.82–1.56 (m, 12 H); MS m/z 469 (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 over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (2:1 hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-d2654a3790124d02b27fa39e681c6f20
Source dataset
uspto-grants-2007_07
Patent number
US07244740B2

Reaction notes

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