Methyl iodide → 7-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine

HRID 1522604ノート

反応式

HRID 1522604 の反応式
[I:1][C:2]1[C:3]2[C:4](=[CH:8][NH:9][N:10]=2)[N:5]=[CH:6][CH:7]=1.I[CH3:12].[C:13](=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.C(#N)C.O>[I:1][C:2]1[C:3]2[C:4](=[CH:8][N:9]([CH3:13])[N:10]=2)[N:5]=[CH:6][CH:7]=1.[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[N:9][N:10]([CH3:12])[C:3]=12

参加物

8

反応物 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 178506553HCID 178506553、化合物

生成物 2

HCID 674696007-iodo-2-methyl-2H-pyrazolo[4,3-b]pyridine収率 14.19%HCID 674704107-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine収率 28.4%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 18373917Acetonitrile--water (1/1)溶媒

実験手順

7-Iodo-2H-pyrazolo[4,3-b]pyridine (100 mg, 0.408 mmol), iodomethane (0.025 ml, 0.408 mmol) and cesium carbonate (266 mg, 0.816 mmol) were combined in DMF (5 mL). The mixture was stirred at room temperature for 1 hour then purified by preparative HPLC eluting with a gradient of 20-70% 10 mmol NH4HCO3 in 20/80 (v/v) water/acetonitrile in 10 mmol NH4HCO3 in water using a Phenomenex Gemini Prep 5 μm C18, 75×30 mm column to give 7-iodo-2-methyl-2H-pyrazolo[4,3-b]pyridine (15 mg, 14.19% yield) and 7-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine (30 mg, 28.4% yield). MS [M+H] found 260.0. 7-Iodo-2-methyl-2H-pyrazolo[4,3-b]pyridine (15 mg, 0.058 mmol), Tris(dibenzylideneacetone)dipalladium(0) (1.326 mg, 1.448 μmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (8.38 mg, 0.014 mmol), 3′-fluoro-6′-methyl-2,2′-bipyridin-4-amine (11.77 mg, 0.058 mmol) and sodium 2-methylpropan-2-olate (16.69 mg, 0.174 mmol) were combined in dioxane (5 mL). The mixture was heated at 120° C. for 2 hours and then purified by preparative HPLC eluting with a gradient of 5-40% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column to afford the title compound as a TFA salt.

後処理

  1. customthen purified by preparative HPLC

出典と根拠

ORDレコード
ord-766285b336e0445dbd68e20fa45a5517
出典データセット
uspto-grants-2015_07
特許番号
US09073918B2

反応ノート

読み込み中…