Water → 7-Chloro-2-(4-fluorophenyl)-3-(4-pyridinyl)pyrazolo[1,5-a]pyridine

HRID 2214929Notes

Reaction equation

HRID 2214929 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.C([Li])CCC.C1(C)C=CC(S([Cl:37])(=O)=O)=CC=1.O>O1CCCC1>[Cl:37][C:15]1[N:10]2[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[C:16]([C:17]3[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=3)=[C:11]2[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 962WaterHCID 73974-Toluenesulfonyl chlorideHCID 98571462-(4-Fluorophenyl)-3-(4-pyridinyl)pyrazolo[1,5-a]pyridineHCID 178418339Butyllithium

Product 1

HCID 98584077-Chloro-2-(4-fluorophenyl)-3-(4-pyridinyl)pyrazolo[1,5-a]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A stirred solution of 2-(4-fluorophenyl)-3-(4-pyridinyl)-pyrazolo[1,5-a]pyridine (from Example 26, 100 mg, 0.346 mmol) in dry tetrahydrofuran (4 mL) was cooled to about −78° C. under N2 and n-butyllithium in hexanes (2.5 M in hexanes, 0.27 mL, 0.7 mmol) was added dropwise. The mixture was stirred at −78° C. for about 30 min and a solution of p-toluenesulfonyl chloride (0.15 g, 0.76 mmol) in dry tetrahydrofuran (1 mL) was added. The mixture was allowed to warm to room temperature over 30 min and was stirred at room temperature for 1 hour. Water was added and the mixture was poured into a separatory funnel. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried using anhydrous magnesium sulfate, filtered and evaporated. Purification by silica gel chromatography yielded the title compound, 0.087 g (78.6%). 1H NMR (CDCl3): δ 8.65 (d, 2H, J=5.8 Hz), 7.55–7.69 (m, 3H), 7.30 (d, 2H, J=5.8 Hz), 7.11–7.21 (m, 1H), 7.04–7.13 (m, 3H). MS (ES+ve): 326 (25, M+3), 323 (50, M+), 290 (100).

Workup

  1. temperatureto warm to room temperature over 30 min
  2. stirringwas stirred at room temperature for 1 hour
  3. additionthe mixture was poured into a separatory funnel
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. customThe combined organic layers were dried
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-7419659bb82f44fc92b74c3c9ff8712a
Source dataset
uspto-grants-2006_09
Patent number
US07109209B2

Reaction notes

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