Water → 6-(2-Fluoropyridin-3-YL)-9-(tetrahydro-2H-pyran-2-YL)-9H-purine

HRID 1042262ノート

反応式

HRID 1042262 の反応式
Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1.O.[F:18][C:19]1[C:24](B(O)O)=[CH:23][CH:22]=[CH:21][N:20]=1.O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:18][C:19]1[C:24]([C:2]2[N:10]=[CH:9][N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][N:6]3[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:23][CH:22]=[CH:21][N:20]=1

参加物

7

反応物 4

HCID 962WaterHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 2735133Sodium Carbonate MonohydrateHCID 27832702-Fluoropyridine-3-boronic acid

生成物 1

HCID 444791786-(2-Fluoropyridin-3-YL)-9-(tetrahydro-2H-pyran-2-YL)-9H-purine収率 53%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A solution of 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (6.00 g, 25.1 mmol) in dioxane (54 mL) was sequentially treated with water (7.2 mL), 2-fluoropyridin-3-ylboronic acid (5.31 g, 37.7 mmol), sodium carbonate monohydrate (9.35 g, 75.4 mmol) and PdCl2(dppf) (0.616 g, 0.754 mmol). The stirred mixture was degassed (alternating vacuum/nitrogen) and heated under nitrogen at 100° C. for 10 h. The mixture was cooled and extracted into EtOAc (500 mL) from water (400 mL). The aqueous layer was extracted with EtOAc (200 mL) and the combined organic extracts were dried (MgSO4), filtered through celite, and concentrated. The crude product was dissolved in a small volume of DCM and purified by flash chromatography (50%→75%→100% EtOAc/hexane) to give 6-(2-fluoropyridin-3-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (3.96 g, 53% yield) as an off-white solid. MS (ESI, pos. ion) m/z: 300.1 [M+H]+

後処理

  1. customThe stirred mixture was degassed (alternating vacuum/nitrogen)
  2. temperatureThe mixture was cooled
  3. extractionextracted into EtOAc (500 mL) from water (400 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (200 mL)
  5. dry with materialthe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered through celite
  7. concentrationconcentrated
  8. dissolutionThe crude product was dissolved in a small volume of DCM
  9. custompurified by flash chromatography (50%→75%→100% EtOAc/hexane)

出典と根拠

ORDレコード
ord-ca2c1484403c4232811207d92731e53e
出典データセット
uspto-grants-2013_10
特許番号
US08557830B2

反応ノート

読み込み中…