Carbon Tetrachloride → N-cyclopentyl-4-[5,7-dichloro-2-(4-fluorophenyl)pyrazolo(1,5-a]pyridin-3-yl]-2-pyrimidinamine

HRID 1796549Notes

Reaction equation

HRID 1796549 reaction equation
[Cl:1][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.C([Li])CCC.C(Cl)(Cl)(Cl)[Cl:36]>O1CCCC1>[CH:18]1([NH:17][C:13]2[N:12]=[C:11]([C:10]3[C:9]([C:23]4[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=4)=[N:8][N:5]4[C:6]([Cl:36])=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=34)[CH:16]=[CH:15][N:14]=2)[CH2:19][CH2:20][CH2:21][CH2:22]1

Participants

5

Reactant 3

HCID 5943Carbon TetrachlorideHCID 102231334-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamineHCID 178418339Butyllithium

Product 1

HCID 10203732N-cyclopentyl-4-[5,7-dichloro-2-(4-fluorophenyl)pyrazolo(1,5-a]pyridin-3-yl]-2-pyrimidinamineYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (100 mg, 0.25 mmol) in anhydrous tetrahydrofuran (5 mL) at −78° C. was added n-butyllithium (0.5 mL of 1.6 M solution in hexanes, 0.8 mmol). The resulting reaction mixture was stirred at −78° C. for 10 minutes, followed by addition of carbon tetrachloride (1 mL) and stirring at −78° C. for additional 20 minutes. The reaction was then quenched by the addition of water. The mixture was extracted with ethyl acetate. The ethyl acetate phase was washed with brine, dried (magnesium sulfate), filtered and concentrated in vocuo. The resulting residue was purified by flash chromatography (1:1 ethyl acetate-hexane) to give 50 mg (45%) of N-cyclopentyl-4-[5,7-dichloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine as a yellow foam. 1H NMR (CDCl3): δ 8.53 (broad s, 1H), 8.06 (d, 1H), 7.63 (m, 2H), 7.15 (t, 2H), 7.05 (d, 1H), 6.27 (d, 1H), 5.17 (d, 1H), 4.35 (m, 1H), 2.0–2.1 (m, 2H), 1.4–1.9 (m, 6H); 19F NMR (CDCl3): δ 112.2; MS m/z 442 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. stirringstirring at −78° C. for additional 20 minutes
  3. customThe reaction was then quenched by the addition of water
  4. extractionThe mixture was extracted with ethyl acetate
  5. washThe ethyl acetate phase was washed with brine
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vocuo
  9. customThe resulting residue was purified by flash chromatography (1:1 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-b9817c1ae8f74c4586561c1f95adcd78
Source dataset
uspto-grants-2006_04
Patent number
US07030134B2

Reaction notes

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