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

HRID 1062869Notes

Reaction equation

HRID 1062869 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 vacuo. 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 vacuo
  9. customThe resulting residue was purified by flash chromatography (1:1 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-032dc276a82d49798f5dcf9a45d6c0ec
Source dataset
uspto-grants-2005_11
Patent number
US06962914B2

Reaction notes

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