Water → N-{4-[5-chloro-7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-N-cyclopentylamine

HRID 1796550Notes

Reaction equation

HRID 1796550 reaction equation
[CH:1]1([NH:6][C:7]2[N:12]=[C:11]([C:13]3[C:14]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)=[N:15][N:16]4[C:21](Cl)=[CH:20][C:19]([Cl:23])=[CH:18][C:17]=34)[CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]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+].O.[CH:84]1([NH2:89])[CH2:88][CH2:87][CH2:86][CH2:85]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:23][C:19]1[CH:20]=[C:21]([NH:89][CH:84]2[CH2:88][CH2:87][CH2:86][CH2:85]2)[N:16]2[N:15]=[C:14]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[C:13]([C:11]3[CH:10]=[CH:9][N:8]=[C:7]([NH:6][CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[N:12]=3)=[C:17]2[CH:18]=1

Participants

7

Reactant 5

HCID 962WaterHCID 2906CyclopentylamineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 10203732N-cyclopentyl-4-[5,7-dichloro-2-(4-fluorophenyl)pyrazolo(1,5-a]pyridin-3-yl]-2-pyrimidinamine

Product 1

HCID 10278127N-{4-[5-chloro-7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-N-cyclopentylamineYield 68%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

To a solution of N-cyclopentyl-4-[5,7-dichloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine (0.04 g, 0.1 mmol) in cyclopentylamine (4 mL) was added racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (25 mg), cesium carbonate (50 mg) and palladium (II) acetate (5 mg). The resulting mixture was stirred at 80° C. for 24 hours. Water was added and the mixture was extracted with ethyl acetate. The ethyl acetate phase was washed with brine, dried (magnesium sulfate), filtered and concentrated in vacuo. The resulting residue was purified by flash chromatography (3:7 ethyl acetate-hexane) to give 30 mg (68%) of N-{4-[5-chloro-7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-N-cyclopentylamine as a yellow foam. 1H NMR (CDCl3): δ 8.00 (d, 1H), 7.82 (s, 1H). 7.61 (m, 2H), 7.15 (t, 2H), 6.23 (d, 1H), 6.06 (d, 1H), 6.00 (s, 1H), 5.11 (d, 1H), 4.35 (m, 1H), 3.95 (m, 1H), 2.0–2.1 (m, 4H), 1.5–1.9 (m, 12H); 19F NMR (CDCl3): δ 113.0; MS m/z 4.91 (M+1).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate phase was washed with brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by flash chromatography (3:7 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-05e09b997c5d4b86ab1e9462db674a73
Source dataset
uspto-grants-2006_04
Patent number
US07030134B2

Reaction notes

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