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

HRID 1797051ノート

反応式

HRID 1797051 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-165136d0bc744885aa6f94a94aed2abf
出典データセット
uspto-grants-2006_04
特許番号
US07034030B2

反応ノート

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