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

HRID 1042262노트

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HRID 1042262 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

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

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온도
100 °C

실험 절차

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]+

후처리

  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)

출처 및 근거

ORD 기록
ord-ca2c1484403c4232811207d92731e53e
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08557830B2

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