Water → HCID 44479178, compound

HRID 1811765Notes

Reaction equation

HRID 1811765 reaction equation
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

Participants

7

Reactant 4

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

Product 1

HCID 44479178HCID 44479178, compoundYield 53%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A solution of 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (1) (6.00 g, 25.1 mmol) in dioxane (54 mL) was sequentially treated with water (7.2 mL), 2-fluoropyridin-3-ylboronic acid (Asymchem Laboratories, Inc., Morrisville, N.C.) (5.31 g, 37.7 mmol), sodium carbonate monohydrate (9.35 g, 75.4 mmol) and PdCl2(dppf) (Strem Chemicals, Inc., Newburyport, Mass.) (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® (diatomaceous earth), and concentrated. The crude product was dissolved in a small volume of DCM and purified by flash chromatography (50% to 75% to 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. 1H NMR (400 MHz, d6-DMSO) δ 9.11 (s, 1H), 8.91 (s, 1H), 8.58 (m, 1H), 8.49 (s, 1H), 7.62 (m, 1H), 5.85 (d, 1H), 4.05 (m, 1H), 3.75 (m, 1H), 2.38 (m, 1H), 2.05 (m, 2H), 1.79 (m, 1H), 1.61 (m, 2H).

Workup

  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® (diatomaceous earth)
  7. concentrationconcentrated
  8. dissolutionThe crude product was dissolved in a small volume of DCM
  9. custompurified by flash chromatography (50% to 75% to 100% EtOAc/hexane)

Sources & evidence

ORD record
ord-3d43c375f6aa44e4a434898fd1dfb17a
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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